Carcinogenesis genetic susceptibility

Stern, M.C. and Conti,C.J. (1996). Genetic susceptibility to tumor progression in mouse skin carcinogenesis. Prog. Clin. Biol. Res. 395,47-55. 

Nairn, R.S., S. Kazianis, L. Della Coletta, D. Trono, A.P. Butler, R.B. Walter and D.C. Morizot. Genetic analysis of susceptibility to spontaneous and UV-induced carcinogenesis in Xiphophorus hybrid fish. Mar. Biotechnol. 3 S24-S36, 2001. 

Major differences exist between species In biotransformation processes. For example, most animal species display either rapid (e.g. hamster) or slow (e.g. rat) acetylation activity, whereas hvimons are endowed with a genetically determined polymorphism (7). Differences In biotransformation activities account for many differences In susceptibility to carcinogenesis. For example. It has been demonstrated that differences In acetylation activity Influence the genotoxicity of aromatic amines (8). 

We are aware too that genetics can play a role in susceptibility. Should one therefore select a sensitive animal model or a resistant one For example, for skin carcinogenesis, the SENCAR mouse is regarded as extremely sensitive to many carcinogens, in particular polycyclic aromatic hydrocarbons. On the other hand, C57 Black mice are insensitive to benzopyrene as an initiator. 

Ishiguro, Y., Ochiai, M., Sugimura, T., Nagao, M., and Nakagama, H. (1999) Strain differences of rats in the susceptibility to aberrant crypt foci formation by 2-amino-l-methyl-6-phenylimidazo-[4,5-b]pyridine no implication of Ape and Pla2g2a genetic polymorphisms in differential susceptibility. Carcinogenesis 20, 1063-1068. 

Hemminki K, Bermejo JL (2007) Constraints for genetic association studies imposed by attributable fraction and familial risk. Carcinogenesis 28 648-656 Hemminki K, Forsti A, Lorenzo Bermejo J (2008) Etiologic impact of known cancer susceptibility genes. Mutat Res 658 42-54... 

Waalkes et al. 1991a), indicating a genetic basis of susceptibility. It has been concluded from other mechanistic studies that the susceptibility of some tissues, e.g., testes and prostate, to cadmium carcinogenesis may be related to the relative lack of metallothionein in these tissues (Waalkes et al. 1989, 1992a, 1993a), which would reduce the capacity of these tissues to detoxify cadmium. 

---