VII 



SUMMARY 869 



tissue environment created by carcinogenic agents contributes towards carcino- 

 genesis by I ) creating an unfavorable environment which stimulates genie altera- 

 tion "initiation" and 2) damaging surrounding tissue to contribute a non-spe- 

 cific stimulus to "promotion". 



The subtle differential factors (genetic) in target tissue (lung, thymus, etc.) 

 which determine the cancerous response have not been demonstrated. There is 

 no evidence that abnormal metabolites are carcinogenic. Normal secretion {e.g., 

 hormones) may, however, be carcinogenic even when secreted at normal levels, 

 indicating that the reaction of the altered target tissue is primary in the car- 

 cinogenic response. 



Hormones may merely "promote" carcinogenesis by inducing the multiplica- 

 tion of cells upon which the carcinogenic imprint (initiation) has already been 

 made. This could apply, however, only to the tissues whose proliferation is nor- 

 mally stimulated by hormones. Or they may cause the growth of normal tissue, 

 preparing it for the action of carcinogenic agents. In other instances {e.g., the 

 induction of leukemia) carcinogenesis by hormones is unrelated to their prolifera- 

 tive stimulus. The neoplasm in certain cases appears to be an outcome of sustained 

 proliferation {e.g., thyroid tumors). The absence of circulating hormone may serve 

 as a carcinogenic stimulus {e.g., pituitary tumors induced by thyroidectomy). 



Cancervirusesmay beof thesame character as those inducing infectious diseases. 

 However, in the induction of certain cancers, the virus might be an accelerant, 

 and not essential for carcinogenesis if other factors are sufficiently potent. If 

 alteration in genie material by carcinogens determines tumorigenesis, viruses may 

 be transmissible "plasmagenes", providing cells with the genie factors altering 

 cellular metabolism via enzymatic derangement. In the "masked" form viruses 

 may have attached themselves to cells so intimately that they are transmitted 

 only during cell (nuclear-mitotic) division. 



Adding confusion to the picture is the fact that "cocarcinogens" augment 

 carcinogenesis, and these may be difficult to detect because independently they 

 do not induce neoplasms. Various inorganic chemicals (Hueper, 1953) have been 

 associated with the induction of cancer {e.g., beryllium, arsenic, nickel, etc.). The 

 role of these and agents such as plastics (Oppenheimer et al., 1952, 1955) in tumori- 

 genesis demonstrates the wide variety of agents whose tumor inducing properties 

 are still to be reconciled with the various well documented modes of carcinogenesis 

 involving viruses, hormones, radiation and specific chemicals (Fig. 67). Inflamma- 

 tory tissue response is still an unclarified and nebulous factor in carcinogenesis. 



In conclusion, cancer is induced by a variety of agents which may be either 

 "initiators" or "promoters" of the process. Continuing growth may or may not 

 be dependent upon the factors necessary for genesis. Presently there is no one hypoth- 

 esis which can be used to explain satisfactorily the various modes of carcinogene- 

 sis. The definition of "cancer" may be changed as more information is acquired. 



Literature p. 8yo 



