AGING AND THE MECHANISMS OF CARCINOGENESIS - SOME PRACTICAL IMPLICATIONS

Two-year protocols are commonly used for long-term assay of chemicals for carcinogenicity. However, in some cases, if animals have been expo sed to tested agent from the young age and sacrificed at the age of 2, an underestimation of the carcinogenic potential of non-genotoxic age nts and tumor promoters is possible. Data available show that exposure to non-genotoxic agents or tumor promoters result in tumor developmen t in older than in young animals. Age-related accumulation of ''premal ignant'' cells in several tissues is here discussed. Accumulation with age of spontaneous mutations or mutations evoked by endogenous mutage ns can induce genome instability and, hence, increase the sensitivity to carcinogens and/or tumor promoters. It seems reasonable to recommed the use of old animals for long-term assay of compounds with suspecte d non-genotoxic and tumor-promoting activity. It may be important to r eevaluate standard two-year protocols for long-term assay for car cino genicity and it is recommended to keep animals for at least 30 months, better until natural death, despite non profitable from an economical point of view it is more reliable.