Kidney Cancer in Male Rats and a2Microglobulin Nephropathy

Alpha(a)-2-microglobulin (a-2mG) associated nephropathy has been evaluated as a mechanism of renal tubular cell carcinogenesis in male rats (16-18). The hypothesis supporting this mechanism is based on the finding that chemicals that induce a-2mG accumulation and renal carcinogenesis in male rats have not been shown to induce kidney tumors in animals that lack the ability to synthesize a-2mG in the liver. However, both data that are consistent and inconsistent with this hypothesis exist (16)....

References

Mechanisms of carcinogenesis and biologically based models for estimation and prediction of risk. In S Moolgavkar, D Krewski, L Zeise, E Cardis, H Moller, eds. Quantitative Estimation and Prediction of Human Cancer Risk. Lyon IARC Scientific Publications, No. 131, 1999, pp 179-237. 2. H Vainio, PM Magee, DB McGregor, AJ McMichael. Mechanisms of Carcinogenesis in Risk Identification. Lyon IARC Scientific Publications, No. 116, 1992. 3. KS Crump, DG Hoel, CH...

Definition Of Nongenotoxic Carcinogens

Nongenotoxic carcinogens are generally considered to be those that do not react, directly or through a reactive metabolite, with nuclear DNA. This can be measured as incapability to form DNA adducts, to induce DNA repair, and to produce a positive response in genotoxicity assays, including mutagenicity tests. Experimentally, genotoxicity is commonly evaluated in a battery of short-term tests using a variety of test systems and endpoints, both in vivo and in vitro (1). When all the short-term...