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，如苋菜花，在小鼠胃肠道（GI-tract）中显示出遗传毒性，尽管它们在啮齿动物中缺乏致癌性。本研究的目的是探讨这种差异是否由于遗传毒性和致癌性研究之间治疗方案的差异。将6种彗星试验阳性的食用色素分别以100 ~ 2000 mg/kg/d的剂量单次和三次灌胃给雄鼠4只，以0.5 ~ 2.5%的剂量在饮水中灌胃6 d。偶氮食物色素单次灌胃后在胃和结肠呈阳性，三次灌胃后呈阴性。饮水中偶氮染料连续给药后，1 ~ 2 d饮水后，偶氮染料对大鼠胃肠道DNA的损伤程度逐渐降低，6 d饮水后恢复到对照水平。另一方面，1,2-二甲基肼（DMH）在灌胃后对结肠和肝脏具有致癌性，三次给药后在这些部位产生DNA损伤。对二甲氨基偶氮苯（DAB）和二甲氨基偶氮苯（DMH）在饲喂和饮用后均对肝脏具有致癌性，但在饲喂或饮用6 d后仍对肝脏具有遗传毒性。因此，我们目前的结果表明，当化学物质在饮用水或饮食中持续给予小鼠时，胃肠道和肝脏的致癌性和遗传毒性的增加趋势与给药时间有很好的相关性。

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.