Microdosimetric and radiation chemical concepts for the interpretation of the biological effectiveness of irradiation processes

Rad~at Phys Chem Vol 18, No 3.4, pp 595-602, 1981 Pnnted m Great Britain

0146-5724/81/090595-08%0200/0 ~ 1981 Pergamon Press Lid

MICRODOSIMETRIC AND RADIATION CHEMICAL CONCEPTS FOR THE INTERPRETATION OF THE BIOLOGICAL EFFECTIVENESS OF IRR~DIATION PROCESSES L. Wlesner W~ssenschaftllch-technasche Beratung und Planung D-5068 Odenthal, Germany, Federal Republlc

ABSTRACT For understandang the iLmats an the effacaency of ionaz~ng radaataons to anactavate macroorganasms durang an arradlataon process, a model has been developed, based on the hypothesas that lavang cells, ancludang macroorganasms, can repaar an a glven tame only a lamated number of DNA defects. Low-LET rad~ataons, used in processang, cause a number of DNA defects, defanltely exceedang the repaar capacaty of laving cells, only an a very small fractaon of all slngle energy deposaon events. Therefore, multaple energy deposltaon events durlng a glven tlme in the sensltlve regaons of llvang cells are necessary for permanently damagang vatal cell functaons as precondatlon of thelr inactlvatlon. Taklng into account the spataal and temporal dlstrlbutaons of energy deposltlon events, the dose-rate becomes an addataon to the integrated dose a factor an radlataon processes, almlng at a certaln reductlon factor of vaable mlcroorganlsms. Thls conclusion as of partlcular amportance for the ~ - i r r a d ~ a t a o n for food preserratlon because the dose-rate is usually faarly low, at least in parts of the product, whale energy and nutrlents, requlred for the repaar of DNA defects, are readaly avallable to macroorganlsms whlch enables them to explolt thelr full repaar capaclty.

KEYWORDS DNA defects; repaar capacaty; lonazang radaataon; ~-arradaataon; mlcroorganasms; food preservatlon; energy deposataon events; dose-rate effects; radaatlon processang ;

THEORIES

OF RADIATION ACTION ON LIVING CELLS

M1croorganasms, as relatavely sample baologacal structures, are popular research ob3ects an radlataon blology, ever sance the macrobaclda~ action of radaataon had farst been descrabed an 1898, only two years after the dascovery of X-rays and natural radaoactlvaty. The real nature of the inactlvatlon process by radlataon, h o w e v e ~ has not yet been clearly recognazed. No doubt, quate a number of theoraes traes to explaan the mechanasm of radaataon actaon on lavang cells an general and on macroorganasms an partacular. But these theoraes usually start from rather formal mathematacal consaderatlons and concentrate on the darect radaataon actlon,

595 RPC Vol 18, No 314-.-N

596 neglecting

L WIESNER the fact that l~vang

cells are c o m p o s e d of up to 90 % water.

The b a s a s for these t h e o r i e s was laad a l r e a d y more than 50 years ago by D e s s a u e r (1922) a n d C r o w t h e r (1924) who p o s t u l a t e d that the d a f f e r e n t survaval curves are due to the n u m b e r of "hats" by e n e r g y d e p o s l t a o n events of r a d l a t l o n w h a c h are r e q u a r e d for the ~ n a c t l v a t a o n of a spec~fac m a c r o o r g a n ~ s m . The formal c o n c e p t i o n of the "hlt" to a s e n s a t a v e t a r g e t v o l u m e w l t h a n a m l c r o o r g a n a s m as the e q u a v a lent to the ~ o n l z a t l o n or e x c a t a t a o n p r o c e s s e s p r o d u c e d b y an e n e r g y d e p o s a t ~ o n event. The h a t s o c c u r s t o c h a s t l c a l l y an a w a y w h l c h can be d e s c r a b e d by a P o a s s o n d l s t r a b u t l o n . Thus at b e c a m e p o s s l b l e to r e c o n s t r u c t any type of survaval curve for m l c r o o r g a n l s m s w h a c h h a d b e e n o b s e r v e d e x p e r l m e n t a l l y , by a s s u m i n g a sultable n u m b e r of h l t s as n e c e s s a r y for ~ n a c t a v a t a o n (Fag. I). ipo 0,8

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The b a s a c h a t t h e o r y has b e e n m o d l f l e d and e x t e n d e d over the years an order to m a l n t a l n its u s e f u l n e s s for the e x p l a n a t l o n of the r e s u l t s of n u m e r o u s e x p e r a m e n tal I n v e s t a g a t a o n s . The D N A was a s s u m e d to be the s e n s l t a v e target for the r a d a a taon actlon. I n d l r e c t r a d a a t a o n e f f e c t s by aons and free r a d l c a l s w h a c h are f o r m e d by e n e r g y d e p o s a t a o n e v e n t s an the n e a g h b o u r h o o d of s e n s a t l v e cell s t r u c t u r e s and react, a f t e r d l f f u s a o n an the cell matrax, w l t h i m p o r t a n t b l o m o l e c u l e s , were taken anto account. F l n a l l y a l t e r n a t a v e a n t e r p r e t a t a o n s of the h l t t h e o r y w e r e p r o p o s e d for the d e s c r a p t a o n of c o m p l e x k a n e t a c p r o c e s s e s u n d e r the a c t a o n of r a d a a t l o n (Hug a n d K e l l e r e r , 1966). N e v e r t h e l e s s , the hat t h e o r y b e c a m e i n c r e a s l n g l y u n s a t i s f a c t o r y for the e x p l a n a t l o n of e x p e r l m e n t a l results. In 1972 the t h e o r y of dual r a d l a t a o n a c t a o n w a s a n t r o d u c e d by K e l l e r e r and Rossl (1972) w h a c h can be c o n s a d e r e d as the f o r m a l a z a t l o n of a r g u m e n t s , farst p r e s e n t e d a l r e a d y in 1946 by Lea (1946) and later on a p p l l e d by N e a r y (1965) to the a n a l y s l s of c h r o m o s o m e a b e r r a t l o n s , t a k l n g T r a d e s c a n t a a m l c r o s p o r e s as model system. Thls t h e o r y w h a c h as b a s e d on m a c r o d o s ~ m e t r a c c o n c e p t s for the e n e r g y d e p o s a t l o n by r a d a a t a o n , p o s t u l a t e s t h a t the f o r m a t i o n of p r a m a r y lesaons is p r o p o r t a n a l to the square of the local e n e r g y c o n c e n t r a t l o n .

Bmlog~cal effectiveness of ~rradmtlon processes

597

In D N A the w e a k e s t b o n d s are p a r t i c u l a r l y e n d a n g e r e d by e n e r g y d e p o s i t i o n e v e n t s of r a d l a t l o n b e c a u s e e n e r g y c a n m l g r a t e along the chaln of these b l o m o l e c u l e s over d ~ s t a n c e s of up to some 10 nm. The transfer p r o b a b l y takes place v l a thermal electrons w h e r e f o r e D N A can b e e n c o n s i d e r e d as a c o n d u c t i o n band. The large n u m b e r of s p o n t a n e o u s l y o c c u r r l n g D N A d e f e c t s d u r l n g the llfe-tlme of cells d e m o n s t r a t e s that they are e q u i p p e d w ~ t h e f f i c a c i o u s and very rel~able r e p a l r m e c h a n l s m s for such d e f e c t s b e c a u s e o t h e r w l s e the cells t h e m s e l v e s and thelr species c o u l d not survlve. W ~ t h o u t g o l n g ~nto the d e t a l l s of the various, rather c o m p l e x r e p a l r m e c h a n l s m s w h i c h are at least p a r t l y c a t a l y z e d by enzyms, taklng p a r t ~n the D N A r e p l ~ c a t l o n process, we have to p o l n t to the fact that the repalr of D N A d e f e c t s is a process, r e q u l r l n g tlme and c o n s u m i n g energy. Therefore, it m u s t be e x p e c t e d that l~v~ng cells are only able to r e p a l r a l l m l t e d n u m b e r of D N A d e f e c t s p e r u n l t of tlme correctly. Thls a s s u m p t l o n s l m u l t a n e o u s l y allows for the survlval as well as for the e v o l u t i o n of a specles: T o o large a n u m b e r of not c o r r e c t l y e l ~ m l n a t e d D N A d e f e c t s d u r l n g the g e n e r a t l o n t~me, relatlve to the n u m b e r of D N A d e f e c t s o c c u r r l n g s p o n t a n e o u s l y u n d e r n o r m a l e n v l r o m m e n t a l cond~tlons, w o u l d r e s u l t in a c o r r e s p o n d l n g l y large n u m b e r of s p o n t a n e o u s mutatlcns w h i c h w o u l d d r a s t l c a l l y reduce the chances for the survival of that species. An o v e r c a p a c ~ t y of the systems for the repalr of D N A d e f e c t s w o u l d on the other h a n d exclude any further d e v e l o p m e n t of the specles, ~nhlblt its a d a p t a t l o n to c h a n g l n g llv~ng conditions, and can, therefore, also r e s u l t ~n ~ts e x t i n c t i o n (Kaplan,1972). These aspects of the p r o b l e m a l t o g e t h e r 3ustlfy the h y p o t h e s l s that the inactlvat~on of m l c r o o r g a n l s m s b y r a d l a t l o n rec~ulres the p r e s e n c e of a n u m b e r of D N A defects in the cells w h l c h e x c e e d s the n u m b e r of defects, the r e ~ a l r m e c h a n l s m s can h a n d l e e f f e c t i v e l y at a n y one tlme. A slmllar h y p o t h e s l s has b e e n p r o p o s e d a l r e a d y some tlme ago by H a y n e s (1966) for the e x p l a n a t l o n of survlval curves of i r r a d l a t e d m l c r o o r g a n l s m s . But there was no follow up of thls study w h l c h s u g g e s t e d that the n u m b e r of r e p a l r e d D N A defects r e a c h e s a s a t u r a t l o n value at h ~ g h doses of h l g h e n e r g y r a d l a t i o n or u l t r a - v l o l e t llght. More r e c e n t l y Goodhead, T h a c k e r and Cox (1978) d l s c u s s e d the p o s s l b l l l t y of a d e c r e a s l n g e f f l c l e n c y of the r e p a l r m e c h a n i s m s w h e n the r a d l a t l o n dose I n c r e a s e s in order to e x p l a l n c e r t a i n d o s e - e f f e c t relatlonshlps. The hypothesls, p r e s e n t e d here, b a s e s the i n a c t l v a t l o n of m ~ c r o o r g a n l s m s by ionlzing r a d l a t l o n on the f r a c t l o n of n o t or not c o r r e c t l y r e p a i r e d D N A defects. L o w L E T - r a d l a t l o n s , as u s e d for p r o c e s s l n g purposes, p r o d u c e a number of D N A d e f e c t s w h l c h c l e a r l y e x c e e d s the n u m b e r of s p o n t a n e o u s l y o c c u r r l n g defects and, t h e r e fore, the c a p a c i t y of the repalr mechanlsms, only in a very small f r a c t l o n of all s~ngle e n e r g y d e p o s l t l o n events. Fig. 2 shows for C o - 6 0 ~ - r a d l a t l o n the p r o b a b l l l t y , that the speclflc energy, as d e f i n e d by the I C R U p d e p o s l t e d in I or 2 events, e x c e e d s ~n a spheracal volume w l t h a d l a m e t e r of 2 ~/n a c e r t a l n value. Such a v o l u m e can be taken as r e p r e s e n t a t l v e at least for m a n y types of bacterla. In about 80 % of the e v e n t s the speciflc e n e r g y is b e l o w 0,02 Gy. As such e v e n t s cause o n l y of the order of one D N A defect, a d e t r l m e n t a l e f f e c t is v e r y unprobable. O n l y in the v e r y rare e v e n t s ~n w h l c h the specaflc e n e r g y ~s v e r y m u c h larger than 0,02 Gy, the e n e r g y d e p o s l t l o n by radlatlon can be e f f e c t l v e towards the ~ n a c t l v a t z o n of m ~ c r o o r g a n l s m s . Thus a large p a r t of the energy, d e p o s z t e d by l o w - L E T - r a d ~ a t l o n in a b l o l o g ~ c a l m a t e r ~ a l is wasted, u n l e s s the m l c r o o r g a n a s m s are h l t by a n u m b e r of e n e r g y d e p o s i t i o n e v e n t s w l t h ~ n a tlme ~ n t e r v a ~ u n s u f f ~ c l e n t for the r e p a l r of those D N A d e f e c t s w h l c h have b e e n c a u s e d by the flrst h l t s d u r l n g a r a d l a t ~ o n exposure. Only then the total n u m b e r of d e f e c t s e x c e e d s the c a p a c l t y of the r e d a c t mecha/11sms.

598

L WIESNER

P r i m a r y l e s ~ o n s o r ~ g a n a t e f r o m the i n t e r a c t i o n of two subleslons, the n u m b e r of w h a c h is a s s u m e d to be p r o p o r t i o n a l to the local e n e r g y c o n c e n t r a t i o n . M e a n w h l l e a g e n e r a l ~ z e d f o r m u l a t l o n of the dual r a d l a t ~ o n a c t i o n t h e o r y has b e e n p r e s e n t e d (Kellerer and Ross~, 1978) w h l c h takes ~nto a c c o u n t that the p r o b a b i l i t y of the a n t e r a c t ~ o n b e t w e e n s u b l e s ~ o n s ~s a f u n c t i o n of thelr d ~ s t a n c e and d e p e n d s therefore not o n l y on the m ~ c r o s c o p ~ c d l s t r ~ b u t ~ o n of e n e r g y d e p o s i t ± o n e v e n t s but also on the g e o m e t r i c p a t t e r n of the s e n s l t ~ v e m a t r i x In the cell. The t h e o r y of dual r a d ~ a t l o n a c t i o n has h a d r e m a r k a b l e success b e c a u s e it allows the e x p l a n a t i o n of o b s e r v e d l ~ n e a r - q u a d r a t ~ e d e p e n d e n c e s of r a d ~ a t l o n e f f e c t s on the a b s o r b e d dose, and of the r a t i o of the two c o m p o n e n t s for d l f f e r e n t r a d i a t i o n q u a l l t ~ e s . It also a c c o u n t s for d o s e - r a t e e f f e c t s ~n the b l o l o g ± c a l a c t i o n of r a d ~ a t l o n w h i c h have f r e q u e n t l y b e e n r e p o r t e d (Hall, 1972) Thus the t h e o r y of dual r a d l a t ~ o n a c t l o n is more and m o r e a c c e p t e d as d e s c r l b ~ n g the m e c h a n i s m , underlyang the d e t a i l e d b a o l o g ~ c a l a c t i o n of ~ o n ± z ~ n g r a d i a t i o n s But e v e n thls t h e o r y is not e n t l r e l y s a t l s f a c t o r y b e c a u s e it does not glve any e x p l a n a t l o n for the large d l f f e r e n c e s in r a d l a t l o n s e n s l t l v ± t y among v a r l o u s types of m l c r o o r g a n l s m s or e v e n among stralns of the same type of b a c t e r l a and for the c o n s l d e r a b l e d e p e n d e n c e of t h e l r r a d l a t ~ o n s e n s l t l v l t y on a m b l e n t cond±tlons. A l s o the m o l e c u l a r t h e o r y (Chadwick and L e e n h o u t s , 1973), l d e n t i f y l n g s u b l e s l o n s w l t h s~ngle s t r a n d b r e a k s of D N A m o l e c u l e s and p r ± m a r y l e s ~ o n s w l t h d o u b l e s t r a n d breaks, does not fulfill this r e q u i r e m e n t . I m p l l c l t l y this t h e o r e t l c a l a p p r o a c h a s s u m e s the d e p e n d e n c e of r a d l a t l o n s e n s l t l v l t y on the a m o u n t or c o n c e n t r a t l o n of DNA in l a v l n g cells. But a g o o d c o r r e l a t l o n of thls k ~ n d does not exlst. Moreover, at has b e e n p r o v e n m o r e r e c e n t l y that e v e n d o u b l e strand b r e a k s ~n D N A m o l e c u l e s do not n e c e s s a r i l y i n a c t ~ v a t e a cell b e c a u s e they can also be r e p a i r e d (Lehmann, 1978).

REPAIR CAPACITY

OF L I V I N G CELLS F O R D N A D E F E C T S

The c a p a b i l i t y of l l v l n g cells to r e p a a r DNA d e f e c t s has to be c o n s l d e r e d the k e y for the u n d e r s t a n d a n g of the e f f e c t s of r a d l a t l o n on m l c r o o r g a n l s m s b e c a u s e o t h e r w l s e at b e c o m e s v e r y d a f f l c u l t to e x p l a a n w h y doses of k ~ l o g r a y s and more are r e q u l r e d for the shelf lafe e x t e n s l o n of food items, s u f f e r l n g from m l c r o b l a l spoilage, or for the i n a c t i v a t i o n of p a t h o g e n s and the s t e r 1 1 1 z a t l o n of m e d l c a l supplles. F o r m a m m a l l a n cells it has b e e n shown that the a p p l l c a t l o n of a dose of I0 m G y of g - r a d l a t l o n already r e s u l t s an m u l t i p l e t r a v e r s a l of cells (Rossl, 1976). M o s £ b a c t e r l a l cells have up to an order of m a g n i t u d e s m a l l e r v o l u m e s than m a m m a l i a n cells. A c o r r e s p o n d i n g l y h i g h e r dose is r e q u l r e d for m u l t l p l e traversal, b u t it still r e m a i n s b e l o w I Gy. The r e l a t l v e l y h a g h doses, r e q u l r e d in r a d a a t l o n p r o c e s s l n g for b l o l o g l c a l a p p l l c a t l o n s also do not become u n d e r s t a n d a b l e if one takes into a c c o u n t that o n l y a small p e r c e n t a g e of the cell m a s s is DNA and that the r a d l a t l o n e n e r g y a b s o r b e d by the m a t r i x is only p a r t l a l l y a v a i l a b l e for p r o d u c a n g D N A d e f e c t s vla i n d l r e c t a c t l o n On the other hand, up to several D N A d e f e c t s are p r o d u c e d in a cell p e r m G y of a b s o r b e d r a d ~ a t l o n energy. M o r e o v e r , the d e f e c t s w h l c h h i g h e n e r g y r a d l a t l o n p r o d u c e s in the double h e l l x of DNA, are by no m e a n s unique. The v e r y n a t u r e of D N A m a k e s thls type of b l o m o l e c u l e an an a q u e o u s m e d a u m an w h l c h it is p r e s e n t in cells, to a r a t h e r u n s t a b l e substance D e f e c t s o r l g l n a t e w l t h h l g h f r e q u e n c y s p o n t a n e o u s l y and the p r e v a i l i n g type of d e f e c t s are strand b r e a k s (Crlne, Verly, 1976), a s t h e y are p r o d u c e d by l o n l z a n g radlatlon. Thls is in a c c o r d a n c e w l t h the g e n e r a l e x p e r l e n c e in r a d l a tlon c h e m a s t r y that i o n l z l n g r a d l a t l o n and other m e a n s for l n l t l a t a n g c h e m l c a l r e a c t a o n s glve rase to c h a n g e s of the some nature b e c a u s e the e n e r g y t r a n s f e r w l t h l n m o l e c u l e s leads flrst to the b r e a k of the w e a k e s t bonds. U n d o u b t e d l y these are the s p o n t a n e a n s l y d l s l n t e g r a t l n g c h e m l c a l bonds.

B~olog~cal effecUveness of n'radmt,on processes

599

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(Gy)

P r o b a h l l l t y that the speclflc e n e r g y e x c e e d s in 1 or 2 e n e r g y d e p o s l t l o n e v e n t s of C o - 6 0 ~ - r a d ~ a t l o n an a s p h e r l cal v o l u m e w l t h ~ d l a m e t e r of 2 ~m a c e r t a l n v a l u e (Kellerer, R o s s l , 1 9 7 1 ) .

A m l c r o o r g a n l s m s llke E s c h e r l c h l a coli w h l c h can be m o d e l l e d a p p r o x a m a t e l y by a sphere w l t h a d l a m e t e r of 2 ~m, Is h l t on an a v e r a g e 0.66 tlmes w h e n ~t is e x p o s e d to an a b s o r b e d dose of iO mGy. As l l v l n g cells are able to p e r f o r m the r e p a l r of m o s t types of D N A d e f e c t s w l t h l n a c o u p l e of mlnutes, one can e s t a m a t e that d o s e rates s u b s t a n t l a l l y h l g h e r than i0 m G y / m ~ n are r e q u l r e d for an e f f l c l e n t m l c r o b l c ~ d a l a c t l o n of low L E T - r a d l a t l o n . Thls ~s in a c c o r d a n c e w l t h m a n y r e s e a r c h r e s u ~ s • n r a d l a t l o n b l o l o g y i n d l c a t l n g that the e f f e c t l v e n e s s of l o w - L E T r a d l a t l o n depends on d o s e - r a t e only up to s e v e r a l G y / m l n (Hall, 1972). For lower dose rates the b ~ o l o g ~ c a l e f f e c t of l o w - L E T r a d l a t l o n per u n l t of a b s o r b e d dose d e c l l n e s and r e a c h e s a c o n s t a n t low value for d o s e - r a t e s b e l o w several 10 -3 G y / m l n A more detailed a n a l y s l s of the d o s e - r a t e effect, t a k l n g into a c c o u n t the s t o c h a s t a c d l s t r l b u t l o n of e n e r g y d e p o s l t l o n e v e n t s of l o n l z ~ n g r a d l a t l o n s , w ~ l l be g l v e n e l s e w h e r e (Wlesner, 1980). As the r e p a l r of D N A d e f e c t s n e e d s n o t o n l y tlme b u t also e n e r g y and b u l l d l n g m a t e r l a l s for the r e c o n s t r u c t l o n of d a m a g e d p a r t s of the D N A hellx, ~t b e c o m e s also u n d e r s t a n d a b l e that the e n v l r o n m e n t a l c o n d l t l o n s i n f l u e n c e the r a d l a t l o n s e n s ~ t l v l t y of m l c r o o r g a n l s m s : The a v a ~ l a b 1 1 1 t y of e n e r g y and b u l l d ~ n g m a t e r l a l s in t h e l r e n v l r o n m e n t d e t e r m l n e s If the r e p a l r m e c h a n l s m s can r e a l l y d l s p l a y thelr full capaclty.

600

L WlZSNE~

In the case of m ~ c r o o r g a n l s m s llke b a c t e r l a the cell m e m b r a n e , m a i n l y c o m p o s e d of p r o t e z n s and Izp~ds, p l a y s an i m p o r t a n t role ~n the p r o c e s s e s by w h i c h the supply of e n e r g y and b u z l d ~ n g m a t e r i a l s to the cell is regulated. L l p l d s are r e a d i l y o x i d i z e d ~n the p r e s e n c e of o x y g e n u n d e r the a c t i o n of radlat~on. Therefore, m e m b r a n e s are e a s i l y d a m a g e d by ~ o n l z l n g radzatlon. As they act as o s m o t i c b a r r i e r b e t w e e n the e x t e r n a l e n v i r o n m e n t and the ~ n t e r n a l p a r t of the cell and as they conta~n m a n y of the e n z y m e s y s t e m s for the e n e r g y m e t a b o l l s m , the t r a n s p o r t c o n d ~ t ~ o ~ t h r o u g h the m e m b r a n e a n d the a v a l l a b ~ l ~ t y of e n e r g y can be altered. Hence the r a d l a t ~ o n e f f e c t s on cell m e m b r a n e s have to be taken ~nto a c c o u n t a d d ~ t l o n a l l y .

CONCLUSIONS

FOR B I O L O G I C A L

APPLICATIONS

OF R A D I A T I O N P R O C E S S I N G

The u n d e r s t a n d l n g of the d e p e n d e n c e of the e f f e c t l v e n e s s of a r a d i a t i o n t r e a t m e n t on the d o s e - r a t e b e l o w some G y / m ~ n ~s p a r t l c u l a r l y of i m p o r t a n c e for the d e s i g n and use of ~ - f a c ~ l ~ t l e s b e c a u s e w ~ t h e l e c t r o n a c c e l e r a t o r s the d o s e - r a t e ~s always s e v e r a l o r d e r s of m a g n i t u d e above th~s llmlt. I n d u s t r l a l ~ - i r r a d ~ a t l o n f a c l l ~ t l e s are u s u a l l y d e s l g r ~ d w l t h the o b 3 e c t ~ v e to a c h i e v e a g o o d p h y s i c a l u t l l l z a t l o n of the r a d l a t l o n energy, e m i t t e d by the sources. For a c h l e v l n g thls o b 3 e c t l v e , v o l u m l n o u s p r o d u c t c o n t a l n e r s on p a l l e t s or ~n s e r v e r a l layers ~n front of the source p l a q u e are I r r a d ~ a t e d at the same tlme. S o p h ~ s t l c a t e d p r o d u c t h a n d l ~ n g s y s t e m s a s s u r e that the a n t e g r a t e d dose, abs o r b e d d u r l n g the w h o l e r a d l a t l o n t r e a t m e n t , v a r l e s o n l y w ~ t h l n r a t h e r n a r r o w llmlts o v e r the goods in one contalner. But the d o s e - r a t e v a r l e s in m o s t d e s l g n s of i n d u s t r l a l ~ - i r r a d l a t l o n f a c 1 1 1 t ~ e s over m o r e than 3 o r d e r s of m a g n l t u d e bet w e e n the d ~ f f e r e n t e x p o s u r e p o s l t l o n s , the t r e a t e d p r o d u c t has to p a s s for abs o r b l n g the r e q u l r e d total dose. Thls is e s p e c l a l l y true for the i r r a d ~ a t l o n of goods w ~ t h r e l a t l v e l y h i g h d e n s l t y (~ 0,4 g / c m 3 ) w h e n the r a d ~ a t l o n ~s s t r o n g l y a t t e n u a t e d w ~ t h ~ n the p r o d u c t b e f o r e ~t r e a c h e s the materlal, l o c a t e d far away from the source plaque. T h e r e the b ~ o l o g ~ c a l e f f e c t p e r u n a t of a b s o r b e d dose w~ll u s u a l l y be c o n s l d e r a b l y lower than ~n p o s ~ t ~ o n s ~n w h i c h the d o s e - r a t e is well above s e v e r a l Gy/m~n. The r e d u c t l o n in the b l o l o g l c a l e f f e c t l v e n e s s of a r a d l a t l o n t r e a t m e n t w h e n a cert a l n f r a c t l o n of the total dose ~s a b s o r b e d at low dose-rates, may be e v e n larger than a n t l c l p a t e d f r o m the f o r e g o l n g dlscusslon There are strong l n d l c a t l o n s that a p r e - ~ r r a d l a t l o n at v e r y low d o s e - r a t e s Increases, at least ~n some m ~ c r o o r g a n ~ m s llke E s c h e r l c h ~ a c o l l , t h e r e p a l r c a p a c l t y for DNA d e f e c t s by the i n d u c t l o n of a soc a l l e d 'SOS repalr' (Radman, 1975; W l t k l n 1976). Hence the h l g h e s t p h y s l c a l u t l l l z a t z o n of the r a d l a t ± o n e n e r g y in an I n d u s t r ~ a l w~h-fac~llty, d e f i n e d by the f r a c t l o n of the total a v a l l a b l e r a d l a t l o n e n e r g y ich is a b s o r b e d in the p r o d u c t to glve the r e q u l r e d m l n l m u m d o s e , s not n e c e s s a r l l y the e q u l v a l e n t of on o p t i m u m solutlon. A lower degree of p h y s l c a l u t 1 1 1 z a t l o n of the r a d l a t l o n e n e r g y m a y i n c r e a s e the b l o l o g l c a l e f f e c t l v e n e s s of the r a d ~ a t l o n t r e a t m e n t p e r dose u n l t and t h e r e w l t h the total dose r e q u l r e m e n t w h e n the f r a c t l o n of the e x p o s u r e at low d o s e - r a t e s can be reduced. In food i r r a d l a t l o n it is p a r t l c u l a r l y d e s l r a b l e to p e r f o r m the t r e a t m e n t w i t h h l g h d o s e - r a t e s and i n t e g r a t e d doses, as low as posslble. The lower the dose the less the o r g a n o l e p t l c p r o p e r t l e s of the p r o d u c t are affected. Flrst of all the o r g a n o l e p t l c p r o p e r t l e s of fat c o n t a l n l n g food items d e t e r i o r a t e r a p l d l y b e c a u s e of the o x l d a t l o n of llplds, i n l t l a t e d by r a d l a t l o n in the p r e s e n c e of oxygen. The o x l d a t l o n p r o c e s s is a c h a l n r e a c t l o n w l t h a y l e l d p e r u n l t of a b s o r b e d dose w h l c h i n c r e a s e s w i t h d e c r e a s l n g dose-rate. These a s p e c t s s t r e n g t h e n the r e q u l r e m e n t to p a y m o r e a t t e n t l o n to d o s e - r a t e s in the d e s i g n of i n d u s t r l a l ~--irrad~atlon fac111tles.

Bmlog~cal effectiveness of Lrradmtmnprocesses

601

Basically the some arguments apply to ~ - and electron b e a m facll~tles in whlch the m l c r o o r g a n l s m s absorb the total radlatlon dose, requlred for thelr inactlvatlon, during repeated exposures, separated from one another by t~me intervals. Between the d~fferent exposures the DNA defects, produced in each exposure, can be repaired, at least partly whereby the blolog~cal effectlveness of the t r e a ~ ment per unit of absorbed radlatlon dose ~s reduced. Such deslgns have been proposed for the treatment of llqu~ds, for example the dlslnfect~on of waste-water and sewage sludge (Holl, Schnelder, 1975). But also ~n ~ - i r r a d ~ a t o r s for research purposes, qu~te often equlpped wlth rather small sources, one should check if the dose-rate in the chosen expoSure poslt~on does not fall short of the llmlt of several Gy/m~n. It may well be that some dlverglng experlmental results whlch have been reported, orlg~nate from neglectlng the dose-rate dependence of the b~olog~cal effectlveness of low-LET rad~atlon. For further quant±flcatlon of the theoretlcal background, presented here, more experlmental data, for example on the frequency of spontaneous DNA effects, on the tlme requirements for the repalr of dlfferent types of DNA defects, on the capacity of repalr mechanlsms In llvlng cells and the influence of envlronmental factors are needed. Thus the theory of radlat~on actlon, assumlng the repalr capaclty for DNA defects as the key to the understandlng of blologlcal effects of lonlzlng radlatlons, polnts out d~rectlons for research in radloblology which have not been taken up so far. Such research will be also useful for the 3udgement on dose-effect relatlonshlps at the extremely low doses and dose-rates whlch are consldered as harmful in radloprotectlon. Hltherto extrapol&tlonsof experlmental results, obtalned at hlgh doses a~ddose-rates, over several orders of magnltude are used for estlmatlng the small effects, resultlng from exposures to very low doses at correspondlngly low doserates, because a dlrect experlmental determlnatlon of such effects is not feaslble. If the slze of any b~ologlcal effect of a rad~atlon exposure depends on the d e ~ i t y wlth whlch DNA defects are produced ~n a llv~ng cell, then such extrapolatlons may overestlmate the effects of doses and dose-rates whxch cause only a small number of addltlonal defects wlth~n the "nolse-level" of spontaneous DNA defects, by orders of magn±tude.

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602

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Lehmann, A.R. (1978). Effects of Ionlzln@ Radlatlon on DNA, Sprlnger-Verlag, Berlln-Heldelberg-New York, 312-334. Neary, G.J. (1965). Int.J.Rad~at.B~ol. 9, 477-502. Radman, N. (1975). Molecular Mechanlsms for Repalr of DNA, part A, Plenum Press, New York, 355-367. Rossl, H.H. (1976). Proc. IAEA Sym~. 'Bzolo~ical and Envlronmental Effects of LowLevel Radlatlon', IAEA, Wlen, 245-251. Wlesner, L. (1980). Proc IAEA Symp.'Comblnat~on Processes in Food Irradlatlon', IAEA, Wlen, in press. Wltkln, E.M. (1976). Bacterlol.Rev. 40, 869-907.