Amacher D E, Turner G N, Ellis J H
Mutat Res. 1981 Sep;90(1):79-90. doi: 10.1016/0165-1218(81)90052-5.
Urine from drug-treated rodents was tested directly in the L5178Y TK+/-leads to TK-/- gene mutation assay for the induction of trifluorothymidine-resistant (TFTR) mutants. 18-h urine samples collected from male CD-1 mice which had been treated with either 2-aminofluorene, cyclophosphamide, or lucanthone were incubated with beta-glucuronidase, then added directly to cultures of L5178Y TK+/- mouse lymphoma cells for 3 h. All 3 urine sources produced significant, dose-dependent increases in the frequency of TFTR mutants compared to normal urine or saline controls. When these same chemicals were tested directly as mutagens in L5178Y TK+/- cells, lucanthone and, to a lesser extent, cyclophosphamide were positive both with or without metabolic activation; and aminofluorene was only positive with activation. These results indicate that the urinary metabolites of aminofluorene, cyclophosphamide, and either the parental molecule or urinary metabolites of lucanthone can readily be detected as mutagens in a mammalian cell assay.
将经药物处理的啮齿动物的尿液直接用于L5178Y TK+/-向TK-/-基因突变试验，以检测三氟胸苷抗性（TFTR）突变体的诱导情况。从经2-氨基芴、环磷酰胺或育亨宾处理的雄性CD-1小鼠收集18小时的尿液样本，与β-葡萄糖醛酸酶一起孵育，然后直接加入L5178Y TK+/-小鼠淋巴瘤细胞培养物中3小时。与正常尿液或生理盐水对照相比，所有3种尿液来源均使TFTR突变体频率显著增加，且呈剂量依赖性。当将这些相同的化学物质直接作为诱变剂在L5178Y TK+/-细胞中进行测试时，育亨宾以及在较小程度上的环磷酰胺在有或无代谢激活的情况下均呈阳性；而2-氨基芴仅在有激活时呈阳性。这些结果表明，在哺乳动物细胞试验中，2-氨基芴、环磷酰胺的尿代谢产物以及育亨宾的母体分子或尿代谢产物都可以很容易地被检测为诱变剂。
