Nongenotoxic carcinogenicity

Bakale G, McCreary RD. 1990. Response of the ke test to NCI/NTP-screened chemicals. I. Nongenotoxic carcinogens and genotoxic noncarcinogens. Carcinogenesis 11 1811-1818. 

TABLE 6.3. Tissues Sensitive to Genotoxic and/or Nongenotoxic Carcinogens... 

Costa M. 1995. Model for the epigenetic mechanism of action of nongenotoxic carcinogens. Am J Clin Nutr 61(suppl) 666S-669S. 

Peters, J.M., Cattley, R.C. Gonzalez, F.J. (1997a) Role of PPAR a in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. 

Woo, Y.-T. and Lai, D.Y., (2010) QSAR analysis of genotoxic and nongenotoxic carcinogens a state-of-the-art overview, in Cancer Risk Assessment Chemical Carcinogenesis from Biology to Standards Quantification (eds G. Hsu and T. Stedeford), John Wiley and Sons, Ltd., Hoboken, N.J., pp. 517-556. 

Jackson MA, Stack HF, Waters MD. 1993. The genetic toxicology of putative nongenotoxic carcinogens. Mutat Res 296(3) 241-277. 

However, these chemicals in general and the drugs in particular are not mutagenic in the Ames or other tests. They are therefore classified as nongenotoxic carcinogens. 

There is some evidence that nongenotoxic carcinogens alter apoptosis, a process that maintains the correct cell number and removes damaged cells, and that this plays a role in their carcinogenicity. As mentioned above, damaged or initiated cells (induced or spontaneous) might represent preferential targets for promotion. James et al. (1998) showed that in rat and mouse hepatocytcs in vitro, MEHP induced DNA... 

Biophores of some tubulin inhibitors were identified by CASE on molecules such as colchicine, podophyllotoxin, and dihydrocombrestatin (see Combes, 2000). These chemicals might act as nongenotoxic carcinogens by being able to bind to tubulin, inducing phenomena such as aneuploidy. 

A single positive result in any assay for genotoxicity does not necessarily mean that the test compound poses a genotoxic hazard to humans (also concern for nongenotoxic carcinogens), although in vivo positive may be considered differently than in vitro positive... 

Uncertainty about its range of predictiveness of nongenotoxic carcinogens... 

Perera FP. Perspectives on the risk assessment for nongenotoxic carcinogens and tumor promoters. Environ Health Persp 1991 94 231-5. 

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