DeMarini D M, Brimer P A, Hsie A W
Environ Mutagen. 1984;6(4):517-27. doi: 10.1002/em.2860060405.
We used the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl-transferase (CHO/HGPRT) assay to determine the cytotoxicity and mutagenicity of a crude coal oil, the neutral fraction of this crude, and the following three subfractions of the neutral fraction: aliphatic, neutral polar, and a subfraction composed of polycyclic aromatic hydrocarbons plus neutral nitrogen heterocyclics. We also studied the cytotoxicity and mutagenicity of a blend of light and heavy coal-derived fuel oils before and after hydrogenation. All seven mixtures were highly cytotoxic to CHO cells, but the addition of S9 reduced the cytotoxicity. Also, hydrogenation reduced the cytotoxicity of the blend of coal-derived fuel oils. Although highly cytotoxic, none of the seven mixtures induced a clear mutagenic response in the CHO/HGPRT assay. However, previous work has shown that all of the mixtures except the aliphatic subfraction and the blend after hydrogenation are mutagenic in the histidine-reversion assay in Salmonella typhimurium. Based on chemical analyses of the mixtures, the differential sensitivity of Salmonella and CHO cells to nonmutagenic cytotoxins, and studies of the neutral fraction to which additional benzo[a]pyrene had been added, we conclude that the disparity between the results in Salmonella and those obtained in the CHO/HGPRT assay is probably due to the much greater sensitivity of CHO cells (relative to Salmonella) to the cytotoxins in these coal oils. This sensitivity, coupled with the low concentrations of mutagens relative to nonmutagenic cytotoxins in the coal oils, prevents exposure of the cells to concentrations of the mutagens in the mixtures that are high enough to be quantified in the CHO/HGPRT assay.
我们采用中国仓鼠卵巢细胞/次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶(CHO/HGPRT)试验,来测定一种粗煤焦油、该粗煤焦油的中性馏分以及中性馏分的以下三个亚馏分的细胞毒性和致突变性:脂肪族、中性极性以及由多环芳烃加中性氮杂环组成的一个亚馏分。我们还研究了轻、重煤衍生燃料油混合物在氢化前后的细胞毒性和致突变性。所有七种混合物对CHO细胞均具有高度细胞毒性,但加入S9可降低细胞毒性。此外,氢化降低了煤衍生燃料油混合物的细胞毒性。尽管具有高度细胞毒性,但这七种混合物在CHO/HGPRT试验中均未诱导出明显的致突变反应。然而,先前的研究表明,除脂肪族亚馏分和氢化后的混合物外,所有混合物在鼠伤寒沙门氏菌的组氨酸回复试验中均具有致突变性。基于对混合物的化学分析、沙门氏菌和CHO细胞对非致突变细胞毒素的差异敏感性,以及对添加了额外苯并[a]芘的中性馏分的研究,我们得出结论,沙门氏菌试验结果与CHO/HGPRT试验结果之间的差异,可能是由于CHO细胞(相对于沙门氏菌)对这些煤焦油中的细胞毒素更为敏感。这种敏感性,再加上煤焦油中诱变剂相对于非致突变细胞毒素的浓度较低,使得细胞无法暴露于混合物中足够高浓度的诱变剂,从而无法在CHO/HGPRT试验中进行定量测定。