868 



THE CARCINOGENIC STIMULUS 



II 



CARCINOGENfC AGENT 



\ 



£ 



ABNORMAL MUTATION -PROVOKING ENVIRONMENT 



INITIATION (SOMATIC MUTATION?) 

 (CARCINOGENIC IMPRINT) 



©•SUSCEPTIBLE 

 ©•GENETICALLY RESISTANT 



PROMOTION BY EITHER CARCINO- 

 GENS, CO-CARCINOGENS, HORMONES, 

 OR VIRUSES (MITOTIC STIMULATION 

 OF ALTERED CELLS) 



GROWTH MAY BE: 



(A) OERENOENT ON INITIATING OR 

 PROMOTING AGENTS (FURTHER 

 MITOTIC STIMULATION?) 



(B)INOEPENDENT OF INITIATING OR 

 PROMOTING AGENTS (AUTONOMY) 



CELLS LACKING 

 ENZYME SYSTEMS 

 CONTROLLING 

 NORMAL FUNCTION 



ESSENTIAL 



ACTIVITY NOW 

 PROLIFERATION 



MECHANISM OF 

 INHERITANCE ? 



ALTERED NUCLEIC ACID 

 I (MUTATED "TRANSMISSIBLE GENE") 



METABOLICALLY 

 DEVIATED PROGENY 

 OF "A" ENZYMIC AL- 

 TERATION ■e'"in "B" 

 (AS COMPARED WITH 

 "E" IN *A')RESULTIN6 

 IN UNRESTRICTED 

 GROWTH 



ALTERED ENZYME 

 CONTROLLED BY 

 MUTATED GENE 



FURTHER GENETIC CHANGE 

 ASSOCIATED WITH AUTONOMY? 

 WITH RESULTING METABOLIC 



DEVIATION ANTIGENIC 



SIMPLIFICATION ? 



METASTATIC 



COMPOSITE SCHEME OF CARCINOGENESIS 



Fig. 67. Chart illustrating a composite scheme of carcinogenesis. 



factors for all if such exist. Neoplasms of different tissues have different "remote" 

 causes even if the change from normal to malignant in all cases is precipitated by 

 a mechanism common to all. Whether or not carcinogenic agents augment a 

 spontaneously occurring process or set into motion a new chain of events is still 

 unknown, although certain induced neoplasms occur spontaneously very rarely. 

 The host influences the response to carcinogenic agents; within individuals of 

 the same species genetic factors may determine divergence of response as great 

 as between species. 



Carcinogenic chemicals may combine with or act upon cellular constituents 

 (genes, plasmagenes, gene-enzyme complex) so that the heritable cellular physiol- 

 ogy is altered in the direction of uncontrolled proliferation, The mechanism 

 remains obscure, although there are suggestions concerning pathway {e.g. com- 

 bination with — SH groups). Ionizing radiations might produce similar cytologic 

 alterations, either by direct action on nuclear constituents, or through chemicals 

 {indirect effects) originating from tissvie, post-irradiation. It is possible that the 



