Induction of DNA damage and its fixation as chromosome aberrations by azo dyes in mouse multiple organs

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We have shown that some azo food dyes, such as Amaranth, show genotoxicity in mouse gastrointestinal tract (GI-tract) using the comet assay, in spite of lack of their rodent carcinogenicity. The purpose of this study is to query whether this discrepancy is due to the difference of treatment schedule between genotoxicity and carcinogenicity studies. Six kind of food dyes that were positive in the comet assay were given to groups of four male ddY by single and triple gavage at 100-2000 mg/kg/day and in the drinking wate at 0.5-2.5% for 6 days. Although azo food dyes were positive in the stomach and colon after single gavage, they were negative after triple dosing. When azo dyes in the drinking water were continuously dosed, they induced DNA damage in the GI-tract after 1-2 day drinking and their induced DNA damage decreased with drinking period and returned to control level after 6 day drinking. On the other hand, 1,2-Dimethylhydrazine (DMH), which is carcinogenic to the colon and liver following to their gavage dosing, yielded DNA damage at these sites after triple dosing. p-dimethylaminoazobenzene (DAB) and DMH, both are carcinogenic to the liver following to feeding and drinking, were still genotoxic in the liver following to 6-day feeding or drinking. Therefore, our present result suggested good correlation between carcinogenicity and increasing tendency of genotoxicity with dosing period in the GI-tract and liver when chemicals are given to mice continuously in the drinking-water or diet.