Comparison of 7 azo dyes and their azo reduction products in the rat and hamster hepatocyte primary culture/DNA-repair assays.
Pursuant to the characterization of species differences in the effects of chemical carcinogens, several studies have demonstrated that hamster hepatocytes are more effective than rat hepatocytes in mediating the metabolic activation of certain chemicals to their genotoxic (i.e., mutagenic) derivatives. In the present investigation, a comparison of the amount of DNA repair induced in rat and hamster hepatocytes by 7 azo dyes and 7 aromatic amine azo reduction products of the dyes was performed using the primary hepatocyte culture/DNA repair (HPC/DR) assay. Congo Red and its azo reduction product, benzidine, were more potent inducers of DNA repair in hamster than in rat hepatocytes, whereas Trypan Blue and its reduction product, o-tolidine, were equipotent in the 2 hepatocyte systems. Evans Blue, another o-tolidine-based dye, elicited a greater DNA-repair response in hamster hepatocytes. The absolute potency of these dyes, however, was much less than their reduction products. o-Aminoazotoluene was the most potent of the dyes tested, and its DNA repair-inducing activity was much greater than that of its azo reduction products, o-toluidine and 2,5-diaminotoluene. Ponceau SX, which is carcinogenic in hamsters, but not in rats, was inactive in both hepatocyte systems. Dimethylaminobenzeneazo-1-naphthalene and its 2-naphthalene congener, as well as the 1- and 2-naphthylamine azo reduction products of these dyes, were more potent in hamster than in rat hepatocytes. However, the DNA repair-inducing activities of the parent dyes could not be entirely accounted for by the potencies of their respective naphthylamine derivatives. Taken together, these findings extend previous observations of the superior metabolic activation capabilities of hamster, relative to rat hepatocytes, and further demonstrate the utility of testing chemicals in both the hamster and rat HPC/DR assays.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D004396:Coloring Agents / Q000633:toxicity*; D006224:Cricetinae; D004260:DNA Repair; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009152:Mutagenicity Tests; D009153:Mutagens; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013329:Structure-Activity Relationship
D001391:Azo Compounds; D004396:Coloring Agents; D009153:Mutagens