858 THE CARCINOGENIC STIMULUS II 



In chickens the "masked virus" is capable of inducing the hemorrhagic disease 

 in newly hatched chicks (inoculation of tumor cells). Furthermore, chickens car- 

 rying non-filterable tumors possess immune bodies against Rous sarcoma. The 

 presence of antibodies against sarcoma or leukosis virus in chickens bearing 

 chemically induced tumors has been used as evidence that these neoplasms possess 

 an antigenic "masked" virus. However, the natural occurrence of such antibodies 

 makes this a tenuous hypothesis. 



Of interest is the adaptation of viruses from one species to another so that a 

 chicken virus becomes "duck" or "turkey" virus, again adaptable to the chicken 

 by inoculation of newly hatched birds (Duran-Reynals, 1942, 1943). 



Quoting from Duran-Reynals (1953), an extremist concerning viral etiology, 

 "the viruses of chicken tumors and leukoses have an epidemiologic behavior, they 

 exert both destructive and proliferative effects on cells, they are capable of varying 

 or mutating, and they have the power to induce immune reactions conducive to 

 solid resistance. These viruses, therefore, behave fundamentally like ordinary 

 viruses. On the other hand, viruses of lesser virulence seem to be the cause of sar- 

 comas developing after injection of chemical carcinogens. These viruses are gener- 

 ally masked and they have antigens in common with those causing the naturally 

 occurring tumors or leukoses. Practically nothing is known concerning epithelial 

 neoplasia, but the scant data available are not incompatible with a virus effect". 



IV. CARCINOGENIC CHEMICALS 



Chemical agents induce cancer in man and animals (Figs. 46-59). That coal tar 

 may be tumor-inducing was a clinical observation which led ultimately to the 

 extraction of carcinogenic- (polycyclic) hydrocarbons (Hieger, 1930; Cook et al., 

 1933); many more were subsequently synthesized to determine chemical con- 

 figurations associated with carcinogenic potency. The phenanthrene structure of 

 both the carcinogenic hydrocarbons and sex hormones, and the chemical similarity 

 of bile acids and cancer-inducing hydrocarbons suggested that similar chemicals 

 formed endogenously in man may be carcinogenic; the search for biologically 

 synthesized carcinogenic hydrocarbons has not been successful up to the present. 



{a) Polycyclic hydrocarbons 



The polycyclic hydrocarbons are "complete" and "independent" carcinogens, 

 since they may both "initiate" and "promote" the induction of neoplasms. The 

 initiating action of the hydrocarbons may be completed by an agent, e.g. croton 

 oil, which is not itself an initiator of carcinogenesis. According to Berenblum and 

 Shubik (1949) the actual tumor yield is determined by the initiating agent, the 

 latent period of carcinogenesis by the "promoting" agent, which may not itself 

 be an initiator, but only a "cocarcinogen" {e.g., croton oil). The initiating process 

 is apparently irreversible, which suggests that the effect of the carcinogen may be 

 mutagenic. 



The carcinogenic hydrocarbons induce neoplasms of diverse tissues (Figs. 47, 48, 

 52) 53> 55, 57, 59), and "direct" contact of the tissue with the intact chemical seems 



