16 p. ALEXANDER AKD Z. M. BACQ 



lesion at least for processes leading to cell death. This is in agreement 

 witli the observation that cells without DNA (red cells or reticulocytes) 

 or anucleate fragments of cells (amoebae, Acetabularia 7nediterranea) show 

 tyjDical radio-lesions. Having eliminated enzymes and DNA, the whole 

 concept that a biologically active entity is involved in the primary 

 jjrocess may have to be abandoned. 



We suggested in 1955 (cf. Bacq and Alexander, 1961) that the increase 

 in enzymatic activity wdiich is so frequently seen in irradiated organisms 

 soon after irradiation f could be explained if radiations broke down 

 internal barriers within the cell — the enzyme release theory. 



Not only is there an intracellular increased enzymatic activity but 

 also a leakage of many enzymes (for instance, DNase, peptidase, two 

 transaminases and two dehydrogenases — for ref. Bacq and Alexander, 

 1961) in the plasma and the urine. Such leakage of enzymes is now well 

 understood as a good but unspecific sign of cellular damage; it can be 

 elicited by anoxia or by drug-poisoning. 



Increased enzymatic activity in cell homogenates or tissue slices of 

 whole organisms can be theoretically explained in three ways (see ref. in 

 Bacq and Alexander, 1961). 



(i) Increased synthesis of the enzyme ; this is the case after irradiation 

 for tryptophane peroxidase in the rat, an adaptative enzyme depending 

 for its regulation on the adrenal cortex. 



(ii) Destruction of an inhibitor. Many enzymes (the DNases and 

 RNases) are known to be inhibited by substances that occur naturally 

 in the cell or in circulating fluids. Feinstein and Ballin (1953) believe 

 that this is the case for a cathepsin. 



(iii) Increased contact lietween enzymes and substrates. De Duve 

 (1958) has conclusively demonstrated that certain granules (called 

 lysosomes) contain a series of enzymes (acid DNase, acid RNase, acid 

 phosphatase, cathepsin, /S-glucuronidase and aryl-sulphatase) which 

 in vitro react poorly or not at all with their specific substrate unless 

 their "membrane" has been damaged by freezing, osmotic imbalance or 

 by mechanical means. One should never forget that the DNase which is 

 in these lysosomes (and also in the mitochondria) has no substrate 

 available on the spot ; it must travel a long way (if we think in molecular 

 distance) and pass through many cytoplasmic barriers and through the 

 nuclear membrane before reaching some DNA. 



& 



t Kecent observations by Libinzon (1959) have shown that in the bone-marrow of 

 rabbits the activity of acid and alkahne rii)onucleases is increased three to five times 

 about one hour after tlie beginning of irradiation (1000 r, y-rays ''^'Co, 15r/min.) The 

 activity of the DNases is increased 50 to 100 per cent one hour after irradiation. 



