ML20058G957

Affidavit of Ej Sternglass.Cumulative Affects of Radioactive Release from Reactors Located in Northern Il Should Be re-evaluated.EPA Min Dose of Radiation Probably Cannot Be Met for Some Local Populations

ML20058G957
Person / Time
Site:	Byron
Issue date:	07/19/1982
From:	Sternglass E DEKALB AREA ALLIANCE FOR RESPONSIBLE ENERGY, SINNISSIPPI ALLIANCE FOR THE ENVIRONMENT (SAFE)
To:
Shared Package
ML20058G822	List: ML20058G816 ML20058G957
References
ISSUANCES-OL, NUDOCS 8208030457
Download: ML20058G957 (14)

Text

r Affidavit of Dr. E.J. Sternglass In support of DAARE/ SAFE Contentions 2 and 2(a)

U.S. Nuclear Regulatory Commission Byron Plant Docket No. 50-454.0L Byron, Illinois 50-455.0L My name is Ernest J. Sternglass. I am Professor of Radiological Physics in the Department of Radiology, University of Pittsburgh, School of Medicine. I have taught radiological' safety, health physics, and the principles of nuclear science at the University of Pittsburgh during the past fifteen years. Prior to this, I carried out research in nuclear and radiation instrumentation at the Westinghouse Research Laboratories for 15 years. In the course of the past 30 years of professional experience, I have published over 100 papers and review articles in the ' area of nuclear instrumentation, nuclear physics, nuclear reactor concepts, and the effects i

of radiation on human health.

I am the author of two books dealing with the subject of the effect of low-level radiation on human health published by Ballantine Books in 1972 and by McGraw-Hill in 1981. I have testified at hearings of the Joint Committee on Atomic Energy of the U.S. Congress on the effects of low-level radiat' ion, as well as at various hearings of State

~

Legislatures on this subject since 1963, as well as at rule making hearings of the U.S. Atomic Energy Commission with regard to the establishment of "As Low as Possible" or ALAP radiation exposures, and those of the EPA that. led to the rules for radiation exposure to the population from all sources in the nuclear fuel cycle (40 CFR Part 190).

As a result,of my own professional experience and recent new findings by other investigators published in the scientific literature, I strongly support the contentions of DAARE/ SAFE in the Byron Operating Licensing Hearings 8208030457 820730 PDR ADOCK 05000454 G

PDR

, that the cumulative effects of radioactive releases from this and other nuclear reactors located within the area of northern Illinois should ba reevaluated before the operating license is granted.

The fundamental reason is that there is a strong likelihood that the presently effective EPA regulations for the maximum dose to any member of the general population from all operations of the nuclear fuel cycle under 40 CFR Part 190 cannot be met for the population in the DeKalb, Rockford 'and Sycamore area. This is particularly serious for the case of the thyroid dose due to radioactive iodine for the most sensitive members of the population, namely the infant and the fetus in the early phases of human development, when the doses are some ten to one-hundred times as great as for.the; typical adult for a given release.

This applies both to normal, routine releases and releases under accident conditions such as occurred at Three Mile Island, and more recently at the Ginna Nuclear Plant near Rochester, New York due to the failure of tubings in the heat exchanger of a pressurized water reactor (PWR) generally similar to the two reactors at Byron. It is particularly serious for residents of the DeKalb area, who are surrounded by six large reactors located at Zion, Byron and Dresden, plus other large plants upwind to the west and southwest. All of these plants affect the milk, food and water-supplies that are the principal vectors for radioactive iodine releases under normal operating conditions, as well as the air which is the principal pathway in the case of accidental air-borne releases such as occurred at Three Mile Island and the Ginna plants.

The seriousness of small doses to the thyroid of the developing infant is due to the recent discovery at the University of Maryland Hospital

' published in the Journal of Pediatrics that thyroid hormone abnormalities appear to be involved in sudden infant death, one of the principal causes of infant mortality in the United States today Thus, a relatively small dose that only affects the hormone function of the thyroid at dose levels far below those needed to appreciably increase the risk of thyroid cancer many years later, and which the present NRC and EPA regulations were originally developed, can lead to a significant increase in the risk of death for the developing infant within a year after birth.

The unanticipated seriousness of small iodine releases previously believed to be harmless is further brought out by recently published studies carried out by Dr. A. Petkau of the Canadian Atomic Energy Laboratory at Pinawa, Manitoba ( ) Dr. Petkau's 1980 paper, a copy of which is enclosed, demonstrates that protracted, low-dose rate exposures are hundreds to thousands of times as damaging to cell-membranes as the same total dose delivered in a short burst, such as occurs for medical exposures or was experienced by the people of Hiroshima and Nagasaki.

These r.ew results, which were_not available when the present NRC and EPA regulations were formulated, indicate that cell-membrane damage due to the production of toxic free-radicals, such as is involved in functional damage to the rapidly growing fetal thyroid, is likely to be hundreds of times more serious than had been anticipated on the basis of earlier studies carried out with brief, high dose-rate exposures.

The net effect of these new scientific discoveries is that they for the first i

time provide a biological mechanism for the explanation of earlier observations by a number of authors that low-level chronic exposures to fresh fission products had a much greater than expected effect on infant mortality, I M. A. Chacon and J.T. Tildon, The Journal of Pediatrics, Vol. 90, pp. 758-760, (November 1981).

A. Petkau, Acta Physiol. Scand., Suppl. 492, pp. 81-90, (1980).

E

s

. prematurity and, underweight births, observations that could not be understood at the time and were thus often discounted.

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With these new discoveries the danger to human health from the combined, cumulative long-term exposures to a large number of sources of fission products in the environment has thus greatly increased, despite the low doses involved, especially for the most vulnerable and therefore critical members of the population.

This presents a previously unrecognized risk of multiple nuclear reactor operations that must be reexamined, especially in an area as densely populated as that of Northern Illinois just west of the Chicago Metropolitan area, containing close to half the entire population of the State of Illinois,~but particularly so for the people in the DeKalb areaandtheimmediatevicinityoftheByronplantlocatedAnky17 miles southwest of the City of Rockford, Illinois.

[

k 4s Ernest J' Sterngl ss, Ph.D.

Professor of Radiological Physics State of Pennsylvania County of Allegheny Subscribed before me this N day of NN w1w 1

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Rad. tion carcinogenesis from a membrane perspect.ive

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(-

.J..r-x AllRAM PETKAU

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.E-y Medical Biophyucs Branch. Whiteshell Nuclear Research Establishment, m.

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PETK AU. A.: Radiation carcinogt nesis from a membrane perspective. Acta Physiol Scand g

y J 7 ".

1950. Suppl. 492;111-90. Medical Biophysics Branch. Whiteshell Nuclear Research Estab-g 6 -.. *: ? i 7 ~ ". P lishment. Atomic Energy of Canada Limited. P nawa. Manitoba. Canada.

h y :,3 ; a

, a 4

(,< 7 - : '

'1..

propagate on their own. These reactions otidize the constituent fatty acids (LH) to ahyl

[

7, Radiation damage in phosphobpid membranes involves free radical chain reactions whien g

i y-i 1.. p '-C... }

radicals (L1 which upon oxygenation. form lipid hydroperosides tLOOHL some of which i

&,s

.y.: v ( A -

absorb light at 232 nm. The respone tR) of these membranes to irradiation from tritium 8

'. f 1..

.s t p.,

(aH) in tntiated water increases with dose (D) in accordance with R=aD*, where l

h 4

'.,].{ S,

m=1.44!0.30 m the absence of superoxide onmutase and 0 8010.14 in its presence. The b _'..$ $[O -? f.

- m parar eter "a" is upressible in terms of the dose rate (ADiati by a=c tad /Atr. where 3O/

n= 1.18:0 d5 in the absence of superoxide dhmutase and 0.8220.cpin its presence. Thus.

i U-i. J g.

R=cD* tad /Atl** uhere the values of m n depend on the presence or absence of the fret 9

I

$p$hih. -;a,%h radical scasenger, superoside dismutase. From this composite relationsh.p. the response h

C i.'.

0.

per annum for 100-250 milliremly is calculable and found to differ qualitatively. that is, in

[

% M..'1[.

the absence of superotide dismutase the response increases whereas in the enzyme's pres.

9

- (M, V l.. - 5 : 37 enee it decreases. The latter trend is reminneent of the correlation between radiation dose

[MQ'wQ rate and the per annum m.ilignant morfahty rate in humans. This coincidence is interesting

{t, t"-

2 in that LOOH are hnked in the hierature to several forms of carcinogenesis, y,

3 N. - hMqs[.c d

4.

. W rM :.. :

by u urds: Membrancs. lipids. lipid peror.idation. cancer, carcinogenesis. environmental C'

radiation effects. free radicah. low dose irradiation. dose rate 4

t, -

p-H:

b 8,JU'. 5 u

Q Q(

^

2 y

a m,{-

The concept that cancer is induced by ensironmen-ieal carcinogens, such as N-hydros-N-acetyl-2 j

tal radiation presuppines a cellular response to low amino 0uorene via free radical processes. The e

Ms dmes of ionizing radiation. It also es okes questions activated products, such as 2-nitroso0uorene.

(

l

- i-w.

-wa fggggsgg about the identity of ceUular targets which powess react with microsomal membranes (Floyd et al.

- g the requisite sensitisity to radiation and about the 1978). as well as with lipids containing carbon-car-ll mechanisms insched. Studies of biomembranes, bon double bonds, and produce tumours (mam-

d. imaged by acute esposuses to radiation. h.ne in.

mary) dhtal to the site of injsetion (Floyd et al.

q i

dicated that these cellular structures are radiation 1977L I urther, lipid hydroperoudes given sub-E sensitn e #Wallach & Weidekamm 1973) and impor.

eut.meously to rats hase Seen observed to produce

(

t..nt lo the sunival ofirradiated celh tYatsin t976; tumours awa/ from the site of injection (Cutter &

Su/uki & Akamatsu 197NL Irradiated lipids undergo Schneider 1974L SpecificaHy. the incidence of changes in compsmiion with a decrease in uoimal mammary e treinomas was 20ri ($/25L of ly mpho-Q n.,.ms m

+

unsaturated fatty acids and phospholipids and an sascomas 16'T N/25) and of other malignancies 89

,.s incicase in pesosidation products (Schu.u / et al.

(2/23L The ability oflipid hydroperoudes to induee d

IWih Minn et al.19 tis; De A Asyar 197N; Hammer tumours away from the injection site is an esample d

s e

A Wdig 1979L The damagmg elfcet of these per.

of damaging action at a distanee and is beliesed to i.4

?

.M oudation products on the biologie.d aetn at) of bacterial transioinung DN A has been described by

}

Piettomgro et.d. t 1977) u ho point out its r eles anee heuauuns used: Normal un;atur.ned tan) acid iLH L tree radicats of I.H: alL>l i1LL alkow lLO L hydro.

to cas einogenesis.

on el.0 t pho'rhohrid. and/or unsaiusated faits Y

.,)

!!! iCbent } e.u s, j 'lo)d et al. t 1976l has L' show n acid hukoperoude it.O()llt peroude it.OOLL tativ

'.T,,

that hpid h)droperoudes actn ate potential chem.

aa.l shma il Lt hsdmyl radieal t OHl.

..t w

... wo..ws y

s 4

w 1

. m &. ye

. h.. B % W W~ w ~f.f.

V. c 2

ggd_

.ne rate and membrane damage which show and many

tise differences. depending on whether Note I: LH may also be osidized to L' by the oxide 7.4 and 7

'ement of protection. based on free radical monoanion radical (0-Hasegawa & Patterson prepahn.

mg b> superoside dismutase is present or 1978) and by singlet osygen ('0. Rawls & van 2

fold or rr aese relationships are used to calculate the Santen 1970h). O may be formed in strongly al.

. per annum iesponse of the membranes as a kaline solutions from 'OH (Hasegawa & Patterson ponent e (Pnsett a

. o of the background radiation dose rate wi.h.

1978) or by the H:O:-driven osidation of liposy-SIUC#

.00-250 millitem/> ear range. It is shown that genoc (Aushima et al. 1977). Neither condi-membran

..n mule dismutase changes this response in a tion was met in our model membrane system.

1. #d#P#

i. acant. qualitative sense.

Singlet oxygen may be formed via the reaction:

Chelack 2LOOH-LHOH + LO%'O: and was presumably was used present in our membrane system to some e. stent.

becausei l VI RlMiiNTAL Oxidation of the unsaturated fatty acids in phos-I'"

"U

\\lo't il not all mammalian membranes contam pholipids leads to the formation of diene conjugated P'"*#"I rhownohpids, many of which contain unsaturated hydroperosides (Reaction 81 which may be moni-M#'* N taus auds. While this unsaturation of lipids within tored at 232-235 nm with molecular estinction

'P'CE#

mh anes confers desirable growth and adaptise coelTieient s between 24Nm28700. depending on added te

'esistics to lidng organisms, it also disposes the unsaturated fatty acid composition and on the P'# P"'"U to usidahou t eactions and sensitisity to relative estent of eis, trans isomerization (Shen.

3'7 x 1(T

' nhanon. Previously, it was shown that damage of stone 197I).

ground.

y,

' a y

I M

water n E'4 Quoride

'- S' Cll.iCil i.

(Cil,),CO - --

[--

/

(8) and amo

\\

/ g f

g g

strument

\\gg 4

C'. W... A.., W..,j_ ~O W"d T

7 *

(AM..p: w. ~gw g e %y-. s,.g.

,. 68.M.f"s,w $.\\

u'

.:- m

. p m'

_-t

1. s

~

oca..o u.ca,

m.'.'

o _'.. l.r M;

- - n. i Ny;- m d e s 9. N 4 ;-) 7. - ; _ s

, 4. 9 n-Y. uca a e, Jg;. -Qj 3 yh.y y.. E '...-

o p,-

-b

)

Y k b

I 5 b3 J!

Radiation carcimovenesis from a membrwie perspective l h i

('O ) attack (Rawls & van Santen 1970b), but these Other non-conjugated diene hydroperoxides may products (Reaction no. 9) do not absorb at 232 nm.

by '"Cs gamma also be produced. particularly after singlet osygen need at decreasmg OOH lismutase a radio.

mteant protection (CH ACO- +'On (9)

CilaCH A 19761. The greater

ped hydroperoside I for by the under.

dose rate with a quartz fibre electroscope provided imtiation, propua-Other conjugated hydroperoxides (trienes. tetra-an average value of 7.312.4 yR/h. Dose rates from represented by f c urse. also be formed if the enes. etc.) may.

tritiated water at the various concentrations were s.

etisely (Gray 1978:

requisite fatty acids are present but they absorb calculated from the specific tritium concentrations y

awls J; van Santen light of longer wavelengths (Shenstone 1971) and In the aqueous phase of samples and its mean ener-l nechanism cf self-uere not a significant feature in our membrane gy per disintegration of 0.0057 MeV. They ranged

'/

asidizes more and sampks.

from 122 grad /h (1.22 gGy/h) to 12.2 rad /h 10.12 f [.

nto hydroperosides The membranes were prepared in triply-distilled Gy/h). After the addition of the tritiated water.

j j W water as previously described (Petkau & Chelack samples were halved with one portion reci:iving I 4

197M from soybean phospholipids (Azolectin*.

M j]I Associated Concentrates. Woodside. Long Island. ug/ml of bovine superoside dismutase (Tru

[

Laboratories. Dallas) with the other serving as the eno.f( L.

iO N.Y.) in which the major components were phos-control. Diene conjugated hydroperoxide formation phatidylcholine, phosphatidylsenne and phos,

of samples was periodically in the two series phatid>letharolamine. Sterols. phosphatidic acid monitored as an increase in absorbance at 232 nm.

g g

and phosphoinositides were present as minor com-Accumulated radiation doses w cre derived frnm the-ponents. Maj r fatty acids present were I n leic g

acid (18 2. 589). oleic acid (18:1.10G) and pal.

calculated dose rates and clapsed time.

($1 Conjugated hydroperoside formation proceeded mit e acid (16:0. 24 G). Of these, only the finoleic most rapidly in membrane samples esposed to the 16) acid can form both conjugated-or nonconjugated. Idest dose rate and in the absence of super i

diene h>droperosides Metalw such as iron. copper dismutase. Fig. I illustrates typical results of hydro-i and manganese. were present to the estent of 84.

ed to li by the oxide 7.4 and 7 ppm (w/wl. respectively. in the membrane peroside formation in tritiated water at two dif-N l

ferent dose rates (0.0122 and 12.2 rad /h)(0.000122d l

pieparations these impurities were diluted a 1101-and 0.122 Gy/h), both in the presence (open sym-O segaw a & Patterson P0.. Rawls & san Told or more thus reducing still further any com-boli and absence telosed symbol) of superoxide dis-nmed in strongiv al-of peiosidation due to metal catalysis mutase. In general, the growth in hydroperosides y

ponent lasegawa & Pattermn Wnscu & Blank 1%2. Khan l970).

ineieased non. linearly with dose as expected from h

W

. osidation of liposy-nee radiation damage in model phospholipid a cham reaction. The relationship bets.een the i

sih. Nedher condi.

meinbranes and their constituent fatty acids is dose amount of hydroperosides formed (R) and the dose

]

l membrane 9 stem.

ime dependent Wead 1952. Petkau 1972. Petkau & (Dr was best.litted at each dose rate by a power -

e ned sia the reauion:

Chelack 1976. Raleigh et al.1977). tritiated water function iTable li. the characteristics of which de- %

em to mme essent.

bewuse a conveniently allowed the relatisely long pended upon whether superoside dismutase w h

and was presuniably um used as a radiation muree in the present study M

absent or pr esent. The best. fitted lines in the former ed fatts acids m phos-tenn in'adiation espenments OM5 dar per es-series corresponding 1o dose rates of 0.000122-12.2 L]

I on ut dwue coninuated peruneno to be siinuNuwush inn at dityerent Jose rad /h <0.OlHHH22-0.122 G>lhi. were used to es-g i wh.ch may be inom,

'"'C'. The tnnaled water tNew F.ngland Nuclear.

tiinate the respective doses which wou!J be es-G specify activity 25 mG!g t93 = 10' Hq/g) wm molecular estmstion added 'to ditTenent aliquois of a fresh membrane peeted to pioduce the same quantit) of diene c 7

- M 7mt. dependme on immen/ation tShen-P' 'P " d!'""

i" d'C

'"""""I "r040'pGlant. & jugated hydroperosides for esample. an amount omposition and on the i

3.7 < itr Uy/ml.) linal concentiation. The back-equis alent to an abmibance increase of 0.04 at 232 h

nm. These estimated Joses are plotted against Jose s

gmund dose rate for samples w ohout innated rate in l'ig. 2. together with the 95'; contidence

{

estinoited with hihium limits. It is noted that the best.litted ime poscisely I,

water wittun them w as fluoode al. aft chips teonnen Dr 11. M. Johnmni conelates the estimated doses with dose rate and i

W and amounted to it 14 gh/h An alter natn e. in.

4 d

also approum'ates the datum point coiresponding to N

shumental meihod of measunng the backgroun

,ggg F

b o.-

/

],.

g T.W"'

• ~ 7FT si.

c~.

m,

~~W&*'*'

~=_.y

___q_

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$4 A. ['ellan V W- *C.~-

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m f

l t

ic ;

03-il 7

8 I

is g

l I !

t t'il l0 r

I si

.02-1 ic e,

E tA l

g 2

/

%'o a

i 3

i so,-

7 lg li l i

g t

/

I/O iI g

3 D

o'.

T 4I l'

. 01=

/

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I e

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i i es e i g 10 r #

I Ii1*.

i Gf i e' t i

-[

I fs 10 s

e t

t t

t 0

2 3

aO

30 to 10 10 Dese Uteal fig. l. Increase in absorbance at 232 nm sersus dose of model phospholipid mem.

Fig. 2. An iltu branes irradiated in the dark at 2TC with tritiated water at two dose rates: left side rate that isr set of curves for 0.0122 rad /h t0.000122 Gy/h) and right side set of curves for 12.2 peroxides in t rad /h (0.122 Gy/h) with E.

e representing the response in which ts equiv; the absence of superoxide dismutase and O. O representing it in the presence or 0.04 in the at-the enzyme at I gg/ml.

timated from i in Fig. l. Equ.

Ihe background dose rate of 19t 14 pR/h (measured the dose for a constant response may be understood d 'i'"8 Of by 1.iF dmimetry). Thus, the quantitative respo_nse as a decrease in efficiency of radiation as the dose

,of the phmphgigid niETnb'hines to irradiation from, rate is increased. In Fig. 3. this decrease in efficien.

tritiated uater appears related to that from en-cy with increasing dose rates is illustrated as a re.

servations on

, uron _ mental radiation. It is also noted that "tre", the duction in the yield of hydroperoxides per unit dose where, beca:

esponent of the power function giving the best. fit.

over a range in dose rates for which camparative coQrv under red line. is of fractional value. This avoids the am.

data from '"Cs irradiations from a previous study rate ekp$ure i

biguity of meaning at m=1 where the dose would (Petkau & Chelack 1976) were available, The com.

exposures at be proportional to the dose rate and increase in parative results are of interest for several reasons:

Bedford &

proportion to the time required for it to accumu-Firstly, they show that with tritiated water as with Barendson l' r

I late.

":Cs. lower dose rates become progressiwir marm 1962). Houe

'the positive correlation between dme rate and elficient. This contrasts with the oft-repeated ob.

j wigyQ Berry lhia-Iable I /*ratecriam ofmembranes by superoride dismurase against tririnted scater (IITC)I

d* '3k3.-( Y' i

Conel..inni bttween.ibsor b.ince change at 232 nm (R) with dose IDI at difTerent dose rates from 'H E2 b ett eta g p s eettse th;u Correlanon according to R=aD*

may be more

[

.\\ mount ol' 'll as !! TO Without superoxide dNnutase With superoude dismutase "T'dT#EIb 1

(Menger et al ft

(.oncentrui..n Dose rate Corr.

Corr 2

[b.af't/t T

ifx hmt.:

t radth) a m

coeff.

a m

coet t.

tritrated warc

l sparsely distr 0

g. y.9 0 noinH9" l536 l.64 0.97 13.9 0.91 0.97 energy from s Mg 30' OAMuu22 6.4 1.24 0.W membrane. i.

$kYi I"'

0 00122 033 1.10 0.W 10' 0.0122 0.u73 1.53 0.W 0.031 OM 0.93 b

~

,~

0.122 0onti 1.91 0.96 0.0041 OE9 0.9x pms of the be ty 0.tuu m lA3 0.98 000o39 036 o.w gs, egep,3c g

1-.-

0onli 0.95 0.W 0om 2 n.95 0.W ume of. memt e&

Laonnd r.nh.onen,.11..Nr.aory determ ned by I.il' doumetry.

~

w ayueous phe f.

osdone i t*ci-o m ny.,na i,,,a.n ni g -

was used m t i

s.

'M f 4

(~

ni ib4 f --. - K.

.s.4 2

)

}. < q"W.u g y pq.

R.. ~~;, ;.h.

..e.;

m

.y.~,

p.c

.... y ;.

, ;. s e.~. -

1..-

...~s..,..

y.

+ -.. ~ -

-c.~.,...

...- --~-.~ ~

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6 d

Radiati<m carcimmenesisfrom a membrane peripective 85

~~

I 2

'O i s

6 l

g 10 2. so,

\\

4 to',~

• ~

' ~ ~, ~ ~ '

• e

\\

' ' ~ ~

a 1

4 O io-3 i

io.

a e'

)

l 4

2l a

n so g

1 d

}.

d i

'OfM ga g3

,g

,g

,n

,a Eto"

-2

-i o

........ m..,st Fie. 2. An illustration of the increase in dose with dose

\\n mem.

, y peroudes in,trnium-trradiated phosp,holipid membr;Lngs.

f I side rare that is required to induce an amount of hvdro-in u hNh is equivalent to an absorbance increase at 232 nm of I

ge of 0 04 in the absence of superoside dismutase. Dom es-

'N y

12 timated from the type of dose-response curves illustrated DCSE RME te. din) j in Fig. I. Equation of line is y=20C" with a correlation i

coettkient of 0.95. Error bars represent the 959 con.

Fig. J. Variation in yield of hydroperosides in model,.

may be understood phospholipid membranes with dose rate. Yield calculated 6dence limits.

.nhation as the dose ar an absorbance change at 232 nm of 0.3. Upper curve:

deere.nc in ellicien-

• Cs irradiation (from Petkau & Chelack 1976); middle

, illustrated.a a re-servations on cell survival as a function of dose rate and lower curves for esposure to tritiated water in the absence and presence of superoside dismutase ti ug/ml).

osioes per unit dose where.. because of. -DNA repair and ce. ll.u. la.r re - respscrively.

u bich comparatne cov.e_ry under well-osygenated conditions. low dose

...i

.m a poesitun study rateypo3 res are less damaging per unit dose than

.n.nlable, l'he com.

esposures at high dose rates thall & Bedford 19M: cise information on the water content of pho3pho.

for sescral seasom:

liedfoid & hiitelell 197h Hall 1972: Kal &

lipio nTJmimines n needed ibr accurate dosimetrv.

nated w ater.n with llarendson 1972: Hornsev 1970. Barry & Cohen Whyt_ matters meanwhile is that both radiation p).i.'P e"J.s eb M!.*

l 'Ni2 ). Honeser. esceptions have hem r n."wd sources elicited the sanic pattern of ueld vmm

he ottacpeated ob.

uith hyp3 sic tumour celk (Hall & Bedford 19% dose rateVig.7)IThirdly. superoside dismutase lleirv l'Xal and with bone mairow stem cells at low veiy sutwtantially decreased the y. ld of diene con-ie Jose rates Wu et al.1975). Sceondly, the low ener-jugated bydroperosides induced by tritiated water.

~

L IItIt g> beta mys emitted by tritium _ are ann:nently lee Thomas et al. (1978) have proposed that supe _roside gg ef fe_ctise than "'Cs garuna ran. However, thn radicals (Op react with licid hydroperosides vu_

l may be more apparent than real because the fatty reaction no.10 to produce the alkosy radicals (LO')

t a'Oid iepoliUf phosphoIipid membianes is non.h i

__ ~ -

w hich are ili Et'ly involved in' the mechannett.6 m,J4

_e i \\lene. ci_et al. _197M) in w hich water in general. and

.w.

_._i which fail _y ac.d. 'aistoudauon n propagated.

9 intiated water in p.uticular must necewarily be F

d' spaisely distributed. Moicoser much of the radiant 0 + 1. OOH-O:+ LO' + HO (10)

M energy fio.m decaying tittium nuclei. resident in the g

membrane, is'1 erm.ted.in_t.he at[iacent aqueous Prop.igation of chain reactions is of particular im-Kf/f 1

i

@.M phase because of the.te_ lain ek long path lencth (~h portance during lone espmures at low dose rates.

-e

,, i umt of the beta particles being emilted, Theiefore, when imtration of osidation ot latly acids to alkyl lew enern waV piUbably depouted per umt sol-radicals tL i h'y ~girimary radicals from Cater'

~

w ume of meinbra_ne_ t.han m a sim_ _d.ir volume of the r.EliGlysis is a relath_.e_l.y infieque.nt.es e.n.t. II)

?.,,..

in.

.l.lIl % !s oise U i(Ise tiIIldt(

At!ci (IINNNN

!O N

!N IN

.N Ik k sImI asN l

u.n used m the dosimetispicultty_rh Mole n'e-

"ould attenuate the piopagation steps and thereb)

-F-q r

s<

g

• M'A l

l

N

~e i

W.

I y, g.

]

+.

-.. w...

r.

f, M.*%.,C:.c:,.. w.we~w n tr---

r w.,n w

.a

.nn

~-

- [.y. y,

.; > ~ w' W.' -

2. -

W c.:.:,U..;.

W.

A c

.n

"w l

l 86 A. PetLmo 7

o S*

extrapolation. Moreover. the energy spectrum of p-background radiation is not equivalent to that of'H.

s

- u,3 The values for 10' pCilmL O.7x 10' Bq/mL) were i.,

also escluded because at this concentration the 1

4E

-osz 3 dose rate dependence of the membrane response sf 3,

diminishes IFig. 2. Petkau & Chelack 1976). With 3

e=

=

M' 1 8 the remaining values of the exponent "m" included E

5 in ihe averaging. mean vaiues or i.44:0.30 and a

f l

~~~~

2 0.80:0.14 were obtained for membranes exposed to I

0 'U $

'H in the absence and presence of superoxide dis-

{

3-1__,

mutase. respectively. Thus. in general, the re-

g

-oss 5 sponse (R) of the membrane to a radiation dose (D) z 5e2 y#

from tritiated water may be expressed in the form.

-Oss R = aD* w here m = 1.4410.30 in the absence of superoxide dismutase and 0.80 : 0.14 in the pres-car ence of the enzyme. From the tabulated values of oeco its iso 875. 200 223 250 the parameter "a" it is seen to vary with the dose ocst we m. mown rate (AD/at) and was evaluated in terms of the y4' 3:

'N

]

Ne. J. Computer computation of the relatise per annum function a=ct AD/At)"(details given in the Appen.

i response of snodel phosphohpid membranes versus dose dis) where "c" is an undetermined constant ( Ap-es r rate uung the relationship: Response =c x(Dose =xtDose N

rate r*. w here. m = 1.44 :0.10 anJ n= 1.lM:O il5 in the ab.

pendio. The mean values of n= 1.18 0 f5 without C-C sence of superoside dnmuta>e tsolid middle knel and superoside dism'atase and 0.32:0.02/ with the tesana

~ '

m=0E010.14 and n=0.8220%in the enzymei presence enzyme. Thus, the radiation response of the mem-tdotted mid6e lincL In each case. the outer hnes rep-branes is expressed as a function of dose and dose y

resent the 959 confidence hmits. SOD = superoxide dis-d% i mutase.

R = c x D'" x t3 D/at)"

(1) 8#V

reduce the length uf the chains Thomas et al.1978).

On the other hand. Fee (19791 has proposed that where m= I.4410.30 and~ n= 1.18:0./3 in the ab-reph tahty superoside radicals reduee transition me;al ions sence of superoside dismutase and m=0.80:0.14

~

de.g. Fe-Fe") which then cataly ze the Fenton and n=%S210.0 pin the presence of the enzyme.

geogr tors reachon: Fe" + H.0 ~ Fe' < 0 H - O H The hy-Equation (1) was used to calculate the relative per diatic dios>l radical LOH) generated might then ini-annum response of phospholipid membranes to a

tiate faity acid oxidation nearby. By seasenging radiation of 'H quality over the 100-250 milliremly S0"#'

i<

superoside radicals, superoside disthu.t.a..se bould~ -- rance in dose late. The results are shown in Fig. 4

'" 8

, lin kes mmbit this sequence of reactions as well1NicCoid together with the 95G contklence limits. The re.

A Feidouch 1%w. Thus, powibihties esist for the sponse of the membrane in the absence and pres-tumg I

en/>me to moderate both the initiation and prop-enee of superoside dismutase is gisen by the lett P. "#

Fat *'

acation reactions of fatty acid peiosidanon which is hand and tight hand ordinate. respectively. The two a

stunulated by soni/mg radiation.

responses are qualitatis ely dif ferent. In the absence trate-Retm nmg once moie to the pow er functions of superoude dismutase the response inercases that hsted in the table it is noted that the esponent "m" with dose rate w heteas. in the presence of the crem shitets m the two senes of measurements being enzy me. it deeieaset Nioicoser. the latter is be-that str generally gieater than one in the absence of tween %4.7 times smaller in magnitude, depend-d0'#

• M supcioside dismutase and lew than one in the ing on the dose sate. The drop.offin response in the for il en/> me s presence. In both series, the values of.

presence of supetoude dismutase is of particular iIIiist

" m.. sary at random. A mean salue for each series interest in that it is the result of protectise tf " -

~

3T.g estm w as therefore calculated. b.ned on the data los mechamsms opeiaung, based on mhibition of free

,3 lu'- In' pCi q.1.7 x IW-3 itP Hqiot tosiated w ater radw.J piocewes by the en/> me. The eneet of this men-per mi. The salues for /ero concentration of tun-protecuon on the iesponse is moie dependent on 2

dGt watei wete escluded beeJuse the) repiesent an dose th.m ou dose iate.

mnu 4

I E

3-l l

y E,. MNN(.?MGE f

k

1. N w ~.- y k ? G. W <- p. f :.4 & V $ % m $ 9 5* C

?y*.". @% f. M % e e g N' y '; q.:. %.m W c xE m a-,...7 @ Q :

7.

f w'u:-

..p gyn:797 y

Radiation carcirwgenesis from a membrane perspective 87 nergy speetrum of go By inference, the foregoing comparison suggests 3 f

.alent to that of 'll.

that caremogenesis is mediated by free radical pro.

j l

s lif Ilgml.) were i o-cesses which are innibitable by antioxidants and/or ll concentration the 5

'N, antiradical acents. The concept of free radical in-J embrane resp. nse

" 'ro -

volvement in chemical carcinocenesis hw been de.

gi lj helack ITM. With 3

l scribed (Stater 19721 Recent electron spin reso-g' j '00{

' nance measurements have demonstrated minimal f5 enent "m" included antioxidant and anti-radical activities in tissue lipids l f' of I.44 -(Un and y*'

during viral carcinogenesis (Hrynevych et al.1976).

@l

[

abranes espwed to of sureroside diw E

As well. in experimental melanomas. maximal 3

) so tumour growth rate is preceded by a reduction m

{

i general. the re-

. radiation dose tD, a

.o-

---

o tissue lipids and by a maximal._ increase in free A

i rewed in the form.

radicals (Bogdanov et al.1978). Hence, there would~

l l

well-defjneIne@or antiradical q

L

~'

m the absence of seem to be a age:Uts in lipid environments. May superoxide dis-I k'

~

0.I4 in the pres-ioo izo iso iso iso zoo 220 mutase serve such a ro!e? The distribution of the

% ll

- bulated salues of sary with the dose enzyme within lipid environments is not well known a

3

"* 4 d in letms of the fie.1 Annual malignant mortality rate (numberflo'lan. at present. However, it is found in erythr'ocyte l l!

hh numi m a human populauon versus background radiation ghosts (Michelson & Durosay 1977) and affects Jhe 3

nen in the Appen-dose rate tarter Frigerio et al.1973). Types of mabgnan-order of fatty acids in tiposomes (Petkau et al.

C',"*

I 8 AP-cies represented are: lung e-o (163,16 4; female breast 1.18:0 /5 without NO 170); hematopoietic a-a t190405t;.ill gastroin.

1979). m. dicating an intimate association with lipids.

shu.08/ with the tesunal 0--O (150-159) and all malignancies x-x. Lipid peroxidation has a radiomimetic effect on Numbers in brackets refer to International Clanification proteins via free radical production (Schaich &

ponse of the mem.

f Death.

Karel 1976; Gardner 1979), so that by inhibiting the n of dose and do e former, superoxide dismutase may modify free radical processes in proteins. These multiple in-DISCUSSION volvements oflipid perosidation with cellular struc-eh Several years ago. Frigerio et al. (1973) sought cor-tures and processes, important to,various forms of tu /5 m the ab-sciations between the incidence of malignant mor-carcinogenesis, make the response of lipid mem-and m anyoto.14 tality in a large human population with a variety of brunes to low-dose. -dose rate radiation interestmg.

ee of the enome, geographic. climatological and socioeconomic fac-particularly that of membranes in which free radi-z tors but, with the exception 'of biickground ra-cal processes are inhibited.

']

ite lhe relatise per diation, failed to lind any. Their data e for cate-Q nd membranes t.,

lin-:50 nullis en gories of cancer which, from the studies discussed M

NOTE ADDED IN PROOF 2

in the mtroduction. have been experimentally se show n m l'ig

' imked to lipid perosidation products, for esample.

Recently. two articles have appeared which bear se lunits. 't hs ie.

alwenee md pie, hunouriof the breastjmd gastrointestmal' tract. are directly on the argument presented here by extend-

. gnen by the lett plotted against background radiation dose rate in it g it to living systems. The first tR. Novak. Pro-j g twth cl>. I he Er l[ig. 5. In both instances. as well as for soine others ccedings of the 18th Hungarian Annual Meeting for p+

i ent. in the.N. se

• 'luded in the ligure, the graphical result illue Biochemistry. Salg6tarjan tl978) $1-53) shows that trates what these authors hase concluded namely, the (Co"") gamma ray dose required to form con-g esponw mue.ne, piescise of the th..t the per annum malignant mojtality r3 de-stant amounts of malondialdehyde in linoleic acid g

i. the latto is be.

ereases with thiiinucaseliidoTe r3teJThey suggest emulsions, human platelets inaitro and in whole-

, J tlut il e latter variable bI' included as a factor in. baly irradet_e,d, murine lher. increases in each case,

c.

saeminde, depend.

as a power fu nction of the dose r, te. The results are 1 fy I m sesponse m the dose-eesponse relaimnship3 pmpost_intto_aecount, jiri qu.jhtuiQ agreement f'"he'r data. The trend of their data. as graphically se w os p.aisul.u

. agreement a no,t_urypyngq_smee malon-g Wustrated m Fig. 5 is qualitatively similar to the. [ This

. ult of piotectn e e7 mated per.mnum reyponye of mir supesoude dialdehyde is a product of the free radical ti 43 i mho. mon of fice t he ettut of this dhmutase pmleM Uph,l_ membranes t hg. 4). Di-reactmns b h polyunsaturated latty acids 4

'"e""""II). this compa ison is based on the per are r'esoudved. The author also shows that. at

{

g

...e A penaent on an optunal dose. superoude dismutase inhibits 44

.mnum iesn nse versus dose rate.

en-Aff d't a Of sJe

[

I Y @.. : W...cf.E.w, T.~ ; M W W M.U? W W W.. M..g.. M.~. i e

~.....,a

i y

.v._w-

,M l

1 n 3. _. f-v. *..

M A. PetLmo

L

.q.

7.9

( -Qi i j,g g.j Tahle 2 f

T. k - ?,N. <

Dose-response relationship E,

'. ' J.9. *1. '; 2 wa -

P.

• <r r*

Dose rate from H Dose rate relationship 8

trad/h)

Equation: R=aD=

Number a=c taDiatra

[D.h....Y).

E Witiremt superrr. tide dismntase G l.w LN f*... ' b.

0.tx10122 R =6.4 D' 8' I

P "U

• M.)-;

0.00122 R=0.33 Di 'a 2

a = cta Dlat r

C.M ;* b' 1 0.0122 R = 0.073 D's=

3 a = cta D/a t r '

• g f

'-A."

(s.122 R =0.00 t l D' "

4 a=ctaDlair

• E M ^M.-*

J., w X 1.22 R=0.00035 D' *2 5

a = ct a Dlat r' '

e'.;,T ;[~4 M Mean : a for mal.44 0.30 Mean : a for n= 1.18:0.15 7 :..., m. -..y.

(

Y=tGQ)h With superu. side dismutase 6,..W..M.'DS 0.0122 R =0.031 D"'

6

,..[ 1:fb'-d 0.122 R = 0.0053 D*

• 7 a =cta Dlat r* "

f.'

1.22 R = 0.00059 Da

• 8 a = ct a D/at r* *

(' '.. M y; d'_.?;p.;

Mean : a for m=0.8010.14 Mean : a for n=0.82:0.N r - n d.., t=

U:;.: '.T. :.

...:.m..'

ry - -

[' lEcE<E M,;I i

radiation-induced malondialdehyde formation in Applying (9) to equations I and 2. we get g

mouse l_iu:r. The second (T. M. Yau. Nicchanisms n in (0.000122&ln 6.4 = In (c)

(10)

~

F.-

v~

a

"'A" of Ageing and Development II (1979) 137-144)

I E M igm shows that malondi;ddehyde is both evtotoxic and and mutacenic in murine L5178Y Ivmr'homa cells. Its mutagenicity with respect to two mdependent

~

n in (0.00122)+ 1n 0.33 = In t e)

(11) l genetic markers. thymidine and methotrexate-Equating the left hand side of equations 10 and 11.

F resistance, is show n to be linearly dependent on the we get M

is strongly implied between the observed muta.

n in (0.000122 ) + In 6.4 = n in (0.00122 ) + 1n 0.33 malondialdehyde dose. Thus a causal relation, hip

~

genesis in L5178Y cells and malondialdehyde, a from w hich n= 1.3. This value is emered in column lipid peroudation product of [rge r, dical reactions 3 above, opposite equation 2. Similarly. equation 1 initiatidI)y%nizing radiation and other agents.-

was used with equations 3-5 to calculate the three The technical awistance of S. D. Pleslach and K. H.

more salues of"n". entered in column 3 above. The WivLe h rnueful'y acknowledged.

values of n are seen to lluctuate between 1.0-1,3.

l The mean value of n = 1.1M10.15 for membranes not pmtected by sure:mide dismutase.

a ppgy ng,g.

Similari). values of n were calculated for mem.

{

I:nupirical derivarium of rehationships lectu ren the hrunes protected by,,uperoside dismutase. using l

unodellipid unconbroute resp <nn e t th. reuliariart Jose equation 6 as Ihe refetence to uhieh the remaining (Di ond Jose unie clD/Att two were indisidually related. The menn value of As discussed in the text. the relationship hetween 11 n = 0.8210.04 and D is gisen by e(=aD"'. wheie the value of"a" Thus. in summary.

R= cD"'( AD/Atr" w here and "m" were determined esperimentally at indi-m = 1.4410.10 n= 1.!S:0.15. in the ab enee of uJual dose rates (see fable 2. columns I and 2L supeioude dismutase and m = 0E0 t o.14 n=

~

9 liom equations 1-5 and (i-5. the paramete "a" is 0.82 to 04 in its piesence.

seen to deeicase monotonically with inercasing J

q dose rate ( AD/1tL Theretone.

• a" must be some b

fundion of AD/At.

M ) Sill M.\\. II.. K \\JIW \\ RT. T.. II A TAN AK A. A..

N \\K \\ r \\NI.11. A lilRtistl. K.1977. Mothficanon 11 aD." = eD*t aDlati ". then a = ellD! At : " and of lipon genase by hsdnigen perouJe and photo-o6d.uion Int J Perfide hotein Res lu-219-225.

' tin f ADlAtl +1n tabln te)

(9p 10:1)! ()RI). J V & st! 1 C111.11. J.11 1c3. q)ose raie 6

.A 5!:'?W,2.W C w$5h& w e M-M h

e%bW_ %e. 5?.y$(%

W"?.IW"W@6@M h h? *

r f._.....-

!G*%%S T4 M. :.t P 6

n m

m;.mm.w;:p.

.e

._,,--_...n.._.

n..e

,g

Radiatism care inumenesis jhwr ce niembrane perspec tit e 89 effects in unchronous mammalian cells in culture.

H ALL. E. J. & BEDFORD. J. S.1964 Dose rate: Its Radianon Research 54:316-327.

BERRY. R. J.196x. Hs pouc protection and recoverv in effect on the survival of Hela cells irradiated with gamma rays. Radiation Research 22: 305-315.

tumour celh arradiated at low dose rates and aucued HALL. E. J. & BEDFORD. J. S.1%6. Estreme hypoua; m mo Br J Radiol 41:921 926.

B ER R Y. R. J. & COH EN. A. B.1962. Some observahons its clTect on the surusal of mammalian cells irradiated at high and low dose. rates. Br J Radiol 30:302-on the reproductise capacity of mammahan tumour 307 celh esposed in viso to gamma radiation at low dose H AMMER. C. T. & WILLS. E. D.19'9 The effect of raret Br J Radiol 35:489 491.

DOGD ANOV. G. N.. GOLOSHCH APOV. A. N. &

iomzmg radiation on the fatty acid composition of SHIOL'KO. V. N.1978. Free radicals as pouible natural fats and on lipid peroside formation. Int J Radiat Biol 35:323-332.

segulators of melanogenesis. Izw Akad Nauk SSSR HASEGAWA. K. & PATTERSON. L. K.1978. Pulse Ser Biol V: 143-147.

g CARROLL. K. K. & KHOR. H. T.1971. EITect oflevel radiolyus studies in model lipid systems: Formation and type of dietary fat on mcidence of mammar) and behasiour of peroxy radicals in fatty acids. Photo-g' chem Photobiol:8:817-823.

tumours mduced in female Sprague. Dawley rats by HORNSEY. S.1970. DJTerences in survival of jejunal L

7.12.dimethylbenztabanthracene. Lipids 6 415420.

CUTLER. M. G. & SCHNEIDER. R.1974. Tumours and crypt cells after radiation delisered at different dose

{W rates. Br J Radiol 43: tiO2-806.

[,

hormonal changes produced in rats by subcutaneous HRYNEVYCH. Yu. P., SYDORYK. Ye. P., BAHLEl.

mjections of linoleic and hydroperoude. Fd Cosmet Ye. A. & YURK!VS'K A. T. M.1976. Oudanse free y[

Toucol 12:4514 59 "C F DE. A. K. & A!Y AR. A. S.1978. Alterations in tinue radical proccues and bio-antioudants in ural car-j cmogenesn Ukr Biokhim Zh 40 615-619.

h hpids of I ts subjec'ed to w hole bods X.irradianon.

K AL. H. B. & B ARENDSEN. G. W.1972. Effects of

'I"'

Suablentherapie 154: 14 t h.

}

cortinuous irradianon at low dose rates on a rat I EE. J. A.1979. On the queshon os superoside tosiat) w thabdomyosarcoma. Br J RaAl 45:279-283.

3 and the biological function ol supero,ude dismutases.

Suhmnied to the Third International Ss mpouum on KH A N. N. A.1970. Smglet states of molecular 09 gen in i

Oudases and Related Oudanon. Reduction Spicms.

hydroperoudahon during opgenahon of oletimc sys-

}

..nors lo and ii held Juh I--3.1979. Alhany. N. Y tems. Oleacineus 23: 2MI-285.

W McCORD. J. & FRIDOVICH.1.1969 Superoude dis-FLOYD. R. A.1977. Free radieak produced by mirow-mutne: An enzi mic funenon for ery throcuprein 11uorcnc. unsaturated lipeJ icaction. Esreuenha 33.

w 197-tw themoeupreinh J lhol Chem-244-6049 6055.

l

, '~I"".'

H.OYD. R.1. SOONG. l.. \\l.. W Al.K ER. R. N. &

ME AD. J. F.1952. The rradiation induced autoudauon 4

or linoleie acid. Science 115:470472.

3 STU AR T. M.1976 Lipid hsdropernude activahon of N-hsdiou N-acettlammolloorene sia a hee radical MENGER. F. M.. JERK U NIC A. J. \\1. A JOHNSTON.

niereil n sommn L u h. c... on i route. Cancer Research 36 2'6l-2767 J. C. Pi?S. l he water content ot'a miecile mierior. The Gord u. reef m#elt J Amer Chem Soc 100:44

, e :.,n ee l l OYD. R. A.. SOONG. L. \\l.. SlU \\R T. M. A 4678 h ul.J c g

g M

. e. I he 3rch Has hem Thophys 134 4 W47 of human cry throes tes bs aetn.ded ongen spGin.

y elu een 19-1.

• I RIGr.RIO. N. A.. ECKl:R \\l \\ N. K. I - A S IOWE.

Photochem Photobiol 23:55-63 mem bi anes n..,

R5 19'1 The Argonne H.id oloocal impact Piopi am Mll.l.f.R. \\. H 19'7. Role of nutution in the etiology of M

7 i T RIPi l' art 1. C.ircmocerne harani hom low-les el.

brease i;anser. Nutrinon 39-2704-2'08 N

low -rate radianon. A NIJI.S.26. Pan I, pp 1 10 I l'. N K.. PHil.l.!PS. I l... K TN f. l.. J. A SMllit.

MIR \\S. C. J.. M ANT 70S. J. D.. LEG \\KIS. N. J. &

3

. nun ne y ;9 c Tumour anJ normal tiwue sesponse to n-LEVIN G. M.196x l'he elleet or ionumg uraJia-h

's t hs :,

saih.inon m s n o Vananon u nth Jes rc.nmg Jose rates non on the brid bioo nthem by thy mus and in er.

h

, ime R.nhanon Research 16.119-127 M

ng.f s,.,,,

R.nhotoes 11- '09 716 M UK Al.1 II. A (W H.DSll:lN. B D 19*6 M u t a-t. \\ M \\1 \\l. l.. G. C ARRt H.I. N N A PI I NKf i T.

gemm of malanaldehule. a Jee. rposdion prosb 11 R pm? Itiests or ihd.os t.a on m.u.im o.

4.n-I M-AhCie ust it peioudvol pok unsaturated talh auds Su-smoeeneus bs

'.12.J une t h s ibe n /ne uiu to as ene m q

bc

.b. s o, e et ens e 19) %Oh9 s ah. Cans et Re sears h 2' l'I7-l'4 2 PE \\RC), M. l..A DAY 10N.S 1971. Inaden c of 1

isu u 14.

n G \\RDNI:R. II. W 19'9 l ar.J h phorcioude seastiuh e.mser m me > on a diet high in polyuntuuratcJ fat.

o Hh prolems and.onmo auds \\seuew j \\erNIood Lanset. M.us h h 46b467 Chem 2* 220-229 O

PLIKTU.

\\. 1972 Elfest of "Na' on a phosphobp J D

(el filCKl. J \\1 1974 lholoptsal sonwynences of mem.

membrane. lle.Jih Ph> ues 22.239-244

-4 be a ns-hpid oudation Pos \\ u s tr a ha n lb.sliem Ye Pf:TK W A. A CHELACK. W. S 1976 Radiort ote s ii t." s g l \\\\ g( g g,

t sN \\I. J l ID M easd H ef ne nt ms mo, o,

.. ~ de a ~ ~.i,, en ~ dei p -

nl i pee l i n s tdat ie to

\\

plk spid fnemhr.ines lh.4him UWpns, \\ g t.l 4II 444-

. ;a e

s

- u J ucima t wm s..e u n,mn

,,,,o seuce a

q i.

11 \\1 1 1 I W ' R.nhanonJosenoe \\ t a tor or inc u.

Pl I K \\1 A K FI I.Y k A 1FPtICK.J R IW

,g

.,c, im m i a.h+,,i. n wJ i.id uohe aps its J R.Jn il u

I' s l *'

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s actmn ol malonaldehyde as a carcinogen. J National w

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g Does SDI) pimide a practical hope for a nuclear agent in humans.

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ihere n a reasonable amount of cuJence that the on membrane pathology as it relates to adenylate

-9 enpio./me superoxide dismut.ne esuaeted f rom eyelase.,

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