Chapter 1 1 

 THE CARCINOGENIC STIMULUS 



Arthur Kirschbanm f 



Multiple factors have been demonstrated to be intimately involved in the genesis 

 of certain neoplasms. Although combined action of specific forces may be neces- 

 sary (Bittner, 1942) the introduction of only a single factor {e.g., a chemical 

 carcinogen) may induce a new growth (Berenblum and Shubik, 1947). 



Influences contributing to carcinogenesis are biological agents, such as hormones 

 (Gardner, 1953; Gardner et al., 1953; Kirschbaum, 1951, 1956, 1957) and viruses 

 (Duran-Reynals, 1953; Beard et al., 1955), chemicals (Wolf, 1952) such as paly- 

 cyclic hydrocarbons, azo dyes, amino compounds, halogenated hydrocarbons, 

 urethane and physical agents like ionizing radiations (Brues, 1954). Although the end 

 results of their action is "autonomous" neoplastic growth, the mode of carcinogen- 

 esis might be different for each class of tumor-inciting agent. However, since 

 chemical, hormonal and physical agents may operate in an additive or even syner- 

 gistic fashion (Furth and Boon, 1943; Kirschbaum et al., 1953) it is probable that 

 the carcinogenic agents involve a common pathway at some point in their action. 



Certain agents are capable only of "initiating" and others of "promoting" car- 

 cinogenesis once initiated (Berenblum and Shubik, 1947). Some combine both 

 properties {e.g. methylcholanthrene) . Continuing neoplastic growth may or may not be 

 dependent upon the action of the incitor (Furth, 1 953) . Control of the growth of certain 

 cancers may be influenced by the administration or withdrawal of agents involved in 

 their genesis, as in the case of estrogenic hormone and breast cancer (Foulds, 1949). 



Perhaps of greatest potential significance is the available information on biolog- 

 ical agents (hormones, viruses) and carcinogenesis. These are apparently in- 

 volved in the developmenl of certain "spontaneous" neoplasms (Bittner, 1942). 

 Specific chemical and physical agents may induce "environmental" cancer; animal 

 experiments indicate that they may potentiate spontaneous (perhaps latent) car- 

 cinogenesis (Andervont, 1938; Heston, 1940; Shimkin, 1940). 



Regardless of the nature of the inciting agents, the host is a prime force in deter- 

 mining carcinogenesis. Within the species genetically controlled response may 

 in one instance reveal the carcinogenic potential of an agent which is innocuous 

 for genetically different members of the same species. Host response may be in- 

 fluenced by non-genetic changes in the "internal environment" effected during 



t Deceased on May 28, 1958, 



Literature p. 8yo 



