Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, UK.
Mutagenesis. 2010 Jul;25(4):327-33. doi: 10.1093/mutage/geq009. Epub 2010 Mar 2.
Sudan-1 and para red are industrial dyes that have been illegally added to some foodstuffs, leading to withdrawal of the adulterated products throughout the UK since 2003. This resulted in international concern that arose because Sudan-1 is classified by International Agency for Research on Cancer as a Category 3 carcinogen. However, little is known about the dose response of this chemical at low, more biologically relevant, doses. The study therefore aimed to characterize the dose response for gene mutation and chromosomal damage induced by two azo dyes, namely Sudan-1 and para red. Gene mutations were analysed using the hypoxanthine phosphoribosyltransferase forward mutation assay and chromosomal damage was measured using the cytokinesis-blocked micronucleus assay. Two cell lines were used in these investigations. These were the AHH-1 cell line, which inducibly expresses CYP1A1, and the MCL-5 cell line derived from a subpopulation of AHH-1 cells that expresses a particularly high level of CYP1A1 activity. The MCL-5 cell line has also been transfected with two plasmids that stably express CYP1A2, CYP2A6 and CYP3A4 and all four of these CYP enzymes are known to metabolically activate Sudan-1. AHH-1 cells were used to investigate the dose response of the azo dyes, and MCL-5 cells were used to see if the dose response changed with increased metabolism. Sudan-1 induced a non-linear dose-response curve for gene mutation and chromosomal damage in AHH-1 cells. The genotoxic activity of Sudan-1 was greatly increased in MCL-5 cells. This indicated that the oxidation metabolites from Sudan-1 were both more mutagenic and more clastogenic than the parent compound. Para red also demonstrated a non-linear dose response for both gene mutation and chromosome damage in AHH-1 cells, and an increase in micronuclei induction was observed after increased oxidative metabolism in MCL-5 cells. Sudan-1 and para red are genotoxic chemicals with non-linear dose responses in AHH-1 but not in MCL-5 cells, and oxidative metabolism increases the genotoxic effect of both compounds.
苏丹红 1 号和对位红是两种工业染料，曾被非法添加到一些食品中，导致自 2003 年以来，全英国所有受污染产品都被下架。这引起了国际社会的关注，因为苏丹红 1 号已被国际癌症研究机构归类为第 3 类致癌物质。然而，对于这种化学物质在低剂量、更具生物学相关性的剂量下的剂量反应知之甚少。因此，本研究旨在描述两种偶氮染料，即苏丹红 1 号和对位红引起的基因突变和染色体损伤的剂量反应。使用次黄嘌呤磷酸核糖基转移酶正向突变试验分析基因突变，使用细胞有丝分裂阻断微核试验测量染色体损伤。在这些研究中使用了两种细胞系。一种是 AHH-1 细胞系，它可诱导表达 CYP1A1；另一种是 MCL-5 细胞系，它源自 AHH-1 细胞的一个亚群，该亚群表达特别高的 CYP1A1 活性。MCL-5 细胞系还转染了两个稳定表达 CYP1A2、CYP2A6 和 CYP3A4 的质粒，所有这四种 CYP 酶都已知能代谢激活苏丹红 1 号。使用 AHH-1 细胞系来研究偶氮染料的剂量反应，使用 MCL-5 细胞系来观察代谢增加是否会改变剂量反应。苏丹红 1 号在 AHH-1 细胞中引起基因突变和染色体损伤的非线性剂量反应曲线。苏丹红 1 号的遗传毒性活性在 MCL-5 细胞中大大增加。这表明苏丹红 1 号的氧化代谢物比母体化合物具有更强的致突变性和更强的断裂能力。对位红在 AHH-1 细胞中也表现出基因突变和染色体损伤的非线性剂量反应，并且在 MCL-5 细胞中氧化代谢增加后观察到微核诱导增加。苏丹红 1 号和对位红是具有非线性剂量反应的遗传毒性化学物质，在 AHH-1 细胞中而不是在 MCL-5 细胞中，氧化代谢会增加这两种化合物的遗传毒性作用。
