IV 



CARCINOGENIC CHEMICALS 865 



Burnett's suggestion that altered antigenicity, which decreases immunologic 

 ability of the host to control tissue growth, is a factor in carcinogenesis. 



Not only do diverse agents produce neoplasms of one tissue, but certain agents 

 are more or less tissvie specific in their carcinogenic action. For example, butter 

 yellow is carcinogenic for only the liver, and then only when the experimental 

 animals are placed on a B-vitamin deficient diet. By its "independent" and 

 unaided action, urethane induces tumors only of the lung. The basis for such 

 specificity is presently unknown. 



An analogy was attempted between the development of malignancy (Wolf, 

 1952) and Lederberg's (1946) findings on adaptative mutation in Neurospora. A 

 mutant strain of this organism may lose the ability to synthesize an amino acid 

 {e.g. leucine) essential for its metabolism. This strain can then survive only if the 

 nutrient, capacity for the biosynthesis of which has been lost, is supplied in the 

 medium. When the nutrient environment becomes unfavorable a new mutation 

 occurs, with a regaining of the ability to synthesize the essential amino acid. The 

 cancer cell is analogous to the Neurospora which, as a result of mutation, is less 

 dependent on its environment, by virtue of mutation having acquired the enzyme 

 systems essential for independence. Haddow (1947) thus "correlates the new and 

 adaptive growth properties of the cancer cell, especially its power of continued and 

 unregulated growth, with the acquisition of a genetic property to synthesize an 

 essential growth factor, or factors, previously supplied from an external source". 



If the effect of carcinogens is cytoplasmic and heritable, "plasmagenes" of the 

 cytoplasm would be acted upon, resulting in chemical (enzymatic) alterations 

 leading to uncontrolled growth. Carcinogens might aflfect plasmagenes in situ and 

 thus hereditarily alter the course of cellular enzyme synthesis and hence growth 

 and differentiation. Cancer viruses might be mutated plasmagenes which can be 

 transmitted from cell to cell. 



V. NUTRITION AND CANCER 



Caloric restriction and other dietary alterations (amino acid deficiency, vitamin 

 deficiency) have been reported as altering the induction of specific neoplasms. 



patible recipients demonstrating that factors other than genetic determine growth of tissue 

 transplants. In this case the endocrine status of the host was very important. 

 Fig. 62. Skin graft into an Fi hybrid mouse. One parent strain was albino. Skin from this 

 strain (s) served as donor for the graft. It is possible to graft either normal or neoplastic 

 tissue from inbred parent stocks into Fi hybrids. Dominant histocompatibility genes deter- 

 mine such tissue compatibility. 



Fig. 63 . Mouse with ascites tumor. The abdominal cavity is distended with fluid within which 

 the neoplastic cells are individually suspended, growing in the fluid medium without stroma. 

 Fig. 64. Anterior chamber intraocular transplants into mice. The transplants of the tumor 

 shown in the eyes of the animal on the right grow temporarily in a foreign strain and regress 

 if the host has been previously untreated. If the host has resisted a previous transplant it is 

 immune to this particular tumor, as demonstrated by the absence of tumor in the eyes of the 

 mouse on the left. 



Fig. 65. Tumor transplant in subcutaneous tissue of tail. Such transplants are valuable for 

 ready amputation of a transplanted tumor (following which immunization occurs in the 

 case of some), or irradiation of a tumor transplant. 



Literature p. 8yo 



