Quantitative analysis of the mutagenicity and carcinogenicity of the low doses of genotoxic carcinogens present in food is of pressing concern. The purpose of the present study was to determine the mutagenicity and carcinogenicity of low doses of the dietary genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 gpt delta transgenic rats were fed diets supplemented with 0, 0.1, 1, 10 or 100 ppm IQ for 4 weeks. The frequencies of gpt transgene mutations in the liver were significantly increased in the 10 and 100 ppm groups. In addition, the mutation spectra was altered in the 1, 10 and 100 ppm groups: frequencies of G:C to T:A transversion were significantly increased in groups administered 1, 10 and 100 ppm IQ in a dose-dependent manner, and the frequencies of G:C to A:T transitions, A:T to T:A transversions and A:T to C:G transversions were significantly increased in the 100 ppm group. Increased frequencies of single base pair deletions and Spi- mutants in the liver, and an increase in glutathione S-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, was also observed in the 100 ppm group. In contrast, neither mutations nor mutation spectra or GST-P-positive foci were statistically altered by administration of IQ at 0.1 ppm. We estimated the point of departure for the mutagenicity and carcinogenicity of IQ using the no-observed-effect level approach and the Benchmark dose approach to characterise the dose-response relationship of low doses of IQ. Our findings demonstrate the existence of no effect levels of IQ for both in vivo mutagenicity and hepatocarcinogenicity. The findings of the present study will facilitate an understanding of the carcinogenic effects of low doses of IQ and help to determine a margin of exposure that may be useful for practical human risk assessment.

中文翻译：

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定量分析F344 gpt delta转基因大鼠中2-氨基-3-甲基咪唑并[4,5-f]喹啉的致突变性和致癌性。

迫切需要对食品中存在的低剂量遗传毒性致癌物的致突变性和致癌性进行定量分析。本研究的目的是确定低剂量饮食中遗传毒性致癌物2-氨基-3-甲基咪唑并[4,5-f]喹啉（IQ）的致突变性和致癌性。给雄性F344 gpt三角洲转基因大鼠饲喂补充了0、0.1、1、10或100 ppm IQ的饮食4周。在10和100 ppm组中，肝脏中gpt转基因突变的频率显着增加。此外，在1、10和100 ppm的组中，突变谱发生了变化：以1、10和100 ppm IQ的组以剂量依赖性方式显着增加了G：C到T：A转化的频率，并且G：C到A：T转换，A：T到T：A转换以及A：T到C：的频率 100 ppm组的G转化率显着增加。在100 ppm中还观察到肝脏中单碱基对缺失和Spi突变体的频率增加，并且谷胱甘肽S-转移酶胎盘形式（GST-P）阳性灶（大鼠肝脏的肝癌前病变）增加。组。相反，通过以0.1 ppm的IQ施用，突变，突变谱或GST-P阳性灶均无统计学变化。我们使用无观察效应水平法和基准剂量法估计了低剂量智商的剂量反应关系，从而估计了智商的致突变性和致癌性。我们的发现表明，对于体内致突变性和肝致癌性，智商均无影响。