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

我们已经证明，一些偶氮食品染料，如阿马兰斯，显示遗传毒性在小鼠胃肠道（GI-道）使用彗星试验，尽管缺乏其啮齿动物致癌性。本研究的目的是质疑这种差异是否是由于遗传毒性和致癌性研究之间的治疗方案差异造成的。将彗星试验呈阳性的6种食用染料以100-2000 mg/kg/d剂量灌胃给雄性小鼠，并以0.5-2.5%的剂量灌胃给雄性小鼠，连续6天。虽然偶氮食品染料在单次灌胃后胃和结肠中呈阳性，但在三次给药后呈阴性。连续饮水中的偶氮染料在饮水后1- 2d引起胃肠道DNA损伤，其损伤随饮水时间延长而降低，饮水后6d恢复到对照水平。另一方面，1，2-二甲基肼（DMH）在灌胃给药后对结肠和肝脏具有致癌性，在三次给药后在这些部位产生DNA损伤。对二甲氨基偶氮苯（DAB）和DMH，都是致癌的肝脏喂养和饮用后，仍然是遗传毒性的肝脏喂养或饮用后6天。因此，我们目前的结果表明，当在饮用水或饮食中连续给予小鼠化学品时，致癌性和遗传毒性增加趋势与胃肠道和肝脏中的给药期之间存在良好的相关性。

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.