0000000000065881
AUTHOR
J.c.s. Clegg
Coordinate mutation and transformation of mouse fibroblasts: induction by nitroquinoline oxide and modulation by caffeine
Mutation and malignant transformation were followed in the same cells. Mouse fibroblasts (C3H 10T 1/2) were mutated and transformed by 4-nitroquinoline-1-oxide with similar, approximately linear dose-responses. The presence of caffeine immediately after exposure to 4-nitroquinoline-1-oxide potently inhibited mutation and transformation at high but not at low doses of 4-nitroquinoline-1-oxide. Whilst the coordinate induction of mutation and transformation could be explained by both a common target (DNA) or a common reactive species hitting several targets, the identical modulation by a DNA repair inhibitor of both end points suggests fundamental similarities in the nature of the lesions lead…
Enzymic Control of Reactive Metabolites from Aromatic Carcinogens
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 rela…