Bacterial mutagenesis and hepatocyte unscheduled DNA synthesis induced by chrysoidine azo-dye components.
5 azo dye components of Gurr chrysoidine 'Y' have been separated, synthesised and identified. Dyes with a methyl substitution (particularly between the two amino groups) were more mutagenic in Salmonella typhimurium strain TA100 with control rat liver S9 than the non-methylated counterpart (range 66-1992 revertants at 50 micrograms/plate). Mutagenicity was also catalysed by human-liver S9 and pre-treatment of rats with either phenobarbitone or beta-naphthoflavone enhanced the activation ability of S9 by greater than 4-fold. Using the most potent promutagenic component (2,4-diamino-3-methylazobenzene), the use of inhibitors of cytochrome P450 (metyrapone: 1.0 mM; alpha-naphthoflavone: 0.075 mM; DPEA: 0.125 mM) and of the flavin monooxygenase (methimazole: 0.75 mM) suggested a major role for cytochrome P448 in the activation of chrysoidine to mutagens. The ability of chrysoidine components to induce unscheduled DNA synthesis in rat hepatocytes in vitro was demonstrated and ranged between 11.92 and 23.5 net nuclear grains at a dose level of 2.5 micrograms/incubation. Since each dye was equi-potent, methyl substitution had little influence on genetic toxicity in hepatocytes.
Sandhu
P
P
School of Biochemistry, University of Birmingham, Great Britain.
Chipman
J K
JK
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004396:Coloring Agents / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008297:Male; D009153:Mutagens; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*
D001391:Azo Compounds; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D009153:Mutagens; C005562:chrysoidine; D010128:p-Aminoazobenzene; D004247:DNA