Increased Production of Mutagenic Metabolites of Carcinogens by Tissues from Senescent Rodents1

Activation of the procarcinogens benzo(a)pyrene and 2-fluorenamine by liver homogenates (S9) prepared from senescent male CFN rats and C57BL/6J mice resulted in an enhanced production of mutagenic metabolites when compared to young rodents, as indicated by an enhancement of the induced re version frequency in a Salmonella typhimurium bioassay. Sim ilar results were observed when carcinogen activation was mediated by purified hepatic microsomes, indicating that the age-related differences in carcinogen activation did not result from aging changes in carcinogen metabolism involving nonmicrosomal mechanisms. The metabolites of many procarcinogens are thought to be the ultimate carcinogens in mammals. Therefore, the present findings are consistent with the hypothesis that some fraction of the markedly increased incidence of neoplasia observed in senescent mammals is a result of age-related alterations in the metabolism of chemical carcinogens.