MECHANISMS OF CHEMICAL RADIATION PROTECTION 309 



oxygen pressure (as measured by electrodes introduced in the fluid 

 surrounding tlie cells)t, it' the time course of tissue anoxia is the same 

 as that of protection, then tlie ])ossil)ihty exists that anoxia is involved 

 as the mode of action of the protector. This is the case for histamine, 

 but not for cysteamine (Van der Meer and van Bekkum, 1959; van der 

 Meer et at., 1959). An antihistamine drug, Phenergan, which abolishes 

 the hypotension and decreases the fall in oxygen tension in the spleen 

 after histamine injection, also decreases the radio-protective effect of 

 the amine. Thus the action of histamine seems to depend on a ph3^sio- 

 logical, not a physico-chemical mechanism. Careful measurements of 

 oxygen tension in tissues have now been made in a number of labora- 

 tories (e.g. Grayevsky in this symposium and van der Meer et al., 1961) 

 and there is complete agreement that SH-protectors do not give rise to 

 a significant reduction in oxygen levels and that, there, radio-j)rotective 

 action cannot be explained by the anoxia hypothesis. 



(c) If a substance protects isolated mammalian cells (thymocytes or 

 reticulocytes) irradiated in vitro when the oxygen pressure does not 

 change, then anoxia is not involved; some mechanism or mechanisms 

 involving free radicals must be at work, which are also probably active 

 in the protection of the whole mammal. Such is the case for cysteamine 

 and cystamine (Nizet et al., 1952; Betz and Booz, 1957; van der Meer 

 and van Bekkum, 1959). On the contrary histamine does not seem to 

 protect isolated mammalian cells in vitro (van der Meer et al., 1959; 

 van der Meer and van Bekkum, 1959), although it has some activity in 

 protecting polymethacrylate in aqueous solution (Alexander, 1953; 

 Alexander e^ «L, 1955). 



(d) At least one test in mammals (extremely rapid increased per- 

 meability of connective skin membranes in rat and man) has been 

 shown to be independent of oxygen and to resx^ond very well to cyste- 

 amine and other protectors (Brinkman and Lamberts, 1960; Bacq et al., 

 1959).:]: 



(e) Several papers have given useful information on the relation 

 between chemical structure and protective power against ionizing 

 radiation in mammals (Bacq and Alexander, 1961; Alexander, 1953; 

 Alexander et al., 1955; Doherty et al., 1957) in the series of cysteamine. 

 The conclusions are the following 



CH2-CH2 



/ \ 



HS NH2 



•j- Anoxia is the consequence of a slowing down of blood circulation and decreased 

 oxygen saturation of capillary blood. 



X According to Brinkman, oxygen decreases this effect of X-rays. 



