Binding of metabolites of dietary 4‐dimethyl‐aminoazobenzene and 2‐methyl‐4‐dimethylamino‐azobenzene to rat liver DNA and protein of subcellular fractions

Abstract

Abstract The binding of metabolites of two related azo dyes of different carcinogenic potency, the carcinogenic 4‐dimethylaminoazobenzene (DAB) and the weakly carcinogenic 2‐methyl‐4‐dimethylaminoazobenzene (2‐Me‐DAB), to rat liver DNA and to subcellular fraction protein was studied following chronic oral administration for 1 to 3 weeks. Different techniques for measuring the amount of DAB metabolites bound to protein were first compared, then the whole study was performed with labelled DAB and 2‐Me‐DAB (aniline ring‐ 14 C) of moderate specific activity. DAB metabolites were bound to liver DNA to a higher extent than those of 2‐Me‐DAB. In contrast, the binding of 2‐Me‐DAB metabolites was equal to or higher than that of DAB metabolites to protein. The amount of protein‐bound metabolites was studied on the nucleo‐mito‐chondrial fraction, microsomes, supernatant, nuclei, chromatin, nucleoplasm, nucleolar fraction and nuclear membrane. Following the administration of both dye diets, the supernatant protein bound the highest level of metabolites. The time‐course of binding of DAB metabolites to DNA and protein was different from that of 2‐Me‐DAB metabolites. These results show the possible involvement of carcinogen‐DNA binding in the mechanism of carcinogenesis.