Genotoxicity in the rodent urinary bladder.

Abstract

Elucidation of the mechanisms by which a chemical may induce urinary bladder tumours in rodents can be expected to provide insight into the relative risk from that agent. The methodologies for exploring whether tumour induction may be a response to direct genotoxic effect of the compound have been successfully applied to the bladders of both mice and rats. Thus, with experimental approaches that utilize adduct detection through the use of immunochemical and postlabelling techniques, unscheduled DNA synthesis and mutagenicity as studied with transgenic animals it is possible to obtain fundamental information on the genotoxic potential of carcinogens in the target bladder. Application of these experimental approaches to carcinogens for which the mechanisms of action are not known should permit assessment of the likelihood that genotoxic or non-genotoxic mechanisms are involved in the tumour induction process. Moreover, such studies may provide knowledge of the molecular pathways that are involved in the action of genotoxic agents, thus enabling judgements to be made as to whether humans are subject to tumour induction by the chemical.