IV CARCINOGENIC CHEMICALS 863 



and irreversible change referrred to by Berenblum and Shubik for the polycyclic 

 hydrocarbons (1949). Gross chromosomal abnormalities result from the adminis- 

 tration of these agents, but the carcinogenic alterations are considered to be more 

 subtle, probably occurring during the "resting" stage of mitosis (Haddow). 



Mutagenic agents are not necessarily carcinogenic, and in Drosophila, although 

 methylcholanthrene appears not to be mutagenic, a melanotic atypical growth 

 occurs more frequently following methylcholanthrene treatment (Burdette, 1955). 

 Strong (1945a, b) has described germinal mutations in mice succeeding the in- 

 jection of methylcholanthrene and thinks that such mutations are correlated with 

 somatic (mutagenic) effects which result in cancer formation. 



(d) Halogenated hydrocarbons 



That chemically unrelated compounds (and physical or hormonal agents, 

 e.g. in leukemia) may induce neoplasms of the same target tissue, is one of the 

 perplexing problems of carcinogenesis. The halogenated aliphatic hydrocarbons 

 which damage the liver, and which are chemically unrelated to the azo dyes, 

 induce hepatic tumors (Edwards, 1941, Eschenbrenner, 1945). Apparently hepatic 

 necrosis is not essential for tumorigenesis, since non-necrotizing doses of carbon 

 tetrachloride may induce hepatic tumors. Thus, the sequence of histologic injury 

 followed by regeneration seems not to be necessarily causally related (Eschen- 

 brenner, 1945). 



[e) Urethane 



Urethane has a simple structure and until recently had been thought to be 

 carcinogenic specifically for the lungs (Nettleship and Henshaw, 1943). However, 

 there is evidence that urethane can contribute to experimental skin carcinogenesis 

 (Salaman and Roe, 1953) and to leukemogenesis (Kirschbaum and Kawamoto, 

 1957). The phases of carcinogenesis may be divided into initiation, promotion and 

 growth in light of the work of Berenblum and others (1949). Agents which 

 complete carcinogenesis {e.g. croton oil), after initiation by a carcinogen {e.g. 

 methylcholanthrene), may be incapable of initiating the process. Apparently 

 urethane may initiate skin carcinogenesis, the supplementary action of a cocar- 

 cinogen {e.g. croton oil) being necessary to complete tumor development. Al- 

 though urethane per se may not be leukemogenic for C57BL mice, it potentiates 

 the leukemogenic action of X-rays or estrogenic hormone, being in this case a 

 tocarcinogen (coleukemogen) . 



Recently Burnett (1956) has suggested that the carcinogenic effect on normal 

 cells is an alteration in antigenicity, perhaps by deletion of "self-markers" so that 

 the controlling influences or "recognition units" are no longer available. The 

 inhibitory effects on tumor growth of chemicals simulating carcinogenic structure 

 could result from such alterations of cellular proteins so that new antigens are 

 formed, which stimulate the formation of antibodies ; thus the control of growth 

 would be by host response. Successful immunization against early transplants of 

 carcinogen-induced tumors within the strain of origin (Foley, 1953) suggests that 

 the induced tumors contain antigens against which the host may react positively 

 from the standpoint of growth inhibition. These results seem to be inconsistent with 



Literature p. 870 



