6533b7dafe1ef96bd126ea99

RESEARCH PRODUCT

Enzymic Control of Reactive Metabolites from Aromatic Carcinogens

subject

description

Mutation and transformation in C3H 10T 1/2 mouse fibroblasts were coordinately induced by 4-nitroquinoline N-oxide and identically modulated by caffeine strongly suggesting mutation as one necessary step in the sequence of events ultimately leading to transformation. The enzymic control of reactive metabolites derived from aromatic carcinogens was then investigated using bacterial mutagenicity as an analytical tool. It was shown that the correlation of bacterial mutagenicity with carcinogenicity of BP and four major metabolites was substantially better when these compounds were activated by intact hepatocytes as compared to commonly used broken cell preparations which suggests that the relatively poor correlation between whole animal carcinogenicity and mutagenicity in the standard Ames assay of BP metabolites was due to differences in metabolism of the compounds in the two systems rather than to differences in the biological end- points, i.e., bacterial mutagenicity versus mammalian carcinogenicity. Addition and removal of cofactors or pure enzymes showed differential involvement in the control of the mutagenically reactive metabolites of the aromatic carcinogens investigated of monooxygenase, epoxide hydrolase, glutathione S-transferase, UDP-glucuronosyltransferase and sulfotransferase.