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首页> 外文期刊>Archives of Toxicology >Effects of chlorohydroxyfuranones on 3-methylcholanthrene-induced neoplastic transformation in the two-stage transformation assay in C3H 10T1/2 cells.
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Effects of chlorohydroxyfuranones on 3-methylcholanthrene-induced neoplastic transformation in the two-stage transformation assay in C3H 10T1/2 cells.

机译：在C3H 10T1 / 2细胞的两阶段转化分析中，氯羟基呋喃酮对3-甲基胆蒽诱导的肿瘤转化的影响。

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摘要

3-Chloro-4-(chloromethyl)-5-hydroxy-2(5 H)-furanone (CMCF), 3-chloro-4-methyl-5-hydroxy-2(5 H)-furanone (MCF) and 3,4-dichloro-5-hydroxy-2(5 H)-furanone (MCA) are chlorination byproducts in disinfected drinking water. These compounds are positive in genotoxicity tests in vitro. We have previously shown that 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5 H)-furanone (MX) can induce malignant transformed foci in the two-stage cell transformation assay in C3H 10T1/2 cells in vitro in both the initiation and promotion phases. In the present study we compared the effects of CMCF, MCF and MCA in the same assay. C3H 10T1/2 mouse embryonic fibroblasts were exposed to these chlorohydroxyfuranones (CHFs) at three different concentrations in the initiation phase or the promotion phase of the assay. In the latter experiments 3-methylcholanthrene (MC, 5 micro g/ml) was used as the initiating chemical. The phorbol ester 12- O-tetradecanoylphorbol-13-acetate (TPA, 0.3 micro g/ml) was used as a positive control promoter. At the end of the assay (6 weeks from the start), the transformation foci were counted and scored after fixation and staining of the cells. When added at the initiation phase of the assay on their own, CMCF and MCF, but not MCA, increased the transformation foci formation. TPA added in the promotion phase did not modify the responses of CMCF and MCF but TPA increased the number of foci in MCA-treated cells. When CHFs were added during the promotion phase to the MC-initiated cells, MCF and MCA enhanced the development of the transformation foci. The effect of CMCF was equivocal since at higher concentrations CMCF actually decreased the number of the MC-induced foci. Including the previous data for MX in this assay and considering the lowest active concentrations, the initiation activity of the foci formation decreased in the order MX >CMCF >MCF, i.e. with the decreasing number of chlorine atoms of the methyl group in the 4-position of the CHF molecule (two, one, and zero, respectively). In contrast, the activity in the promotion phase did not follow the same pattern. MX, MCF and MCA were all active over the same concentration range. Hence, in addition to MX, MCF and MCA may also possess some potential to promote tumor development.
机译：3-氯-4-（氯甲基）-5-羟基-2（5 H）-呋喃酮（CMCF），3-氯-4-甲基-5-羟基-2（5 H）-呋喃酮（MCF）和3， 4-二氯-5-羟基-2（5 H）-呋喃酮（MCA）是消毒饮用水中的氯化副产物。这些化合物在体外遗传毒性测试中呈阳性。先前我们已经证明3-氯-4-（二氯甲基）-5-羟基-2（5 H）-呋喃酮（MX）可以在体外C3H 10T1 / 2细胞的两阶段细胞转化测定中诱导恶性转化灶在启动阶段和晋升阶段。在本研究中，我们在同一试验中比较了CMCF，MCF和MCA的作用。在测定的起始阶段或促进阶段，将C3H 10T1 / 2小鼠胚胎成纤维细胞以三种不同浓度暴露于这些氯羟基呋喃酮（CHF）。在后面的实验中，将3-甲基胆蒽（MC，5微克/毫升）用作引发剂。佛波醇酯12-O-十四烷酰佛波醇-13-乙酸酯（TPA，0.3μg/ ml）用作阳性对照启动子。在测定结束时（从开始算起的6周），在固定和染色细胞后对转化灶进行计数和评分。当在测定的起始阶段单独添加时，CMCF和MCF而不是MCA会增加转化灶的形成。在促进阶段添加的TPA不会改变CMCF和MCF的反应，但TPA会增加MCA处理的细胞中病灶的数量。在促进阶段向MC起始细胞中添加CHF时，MCF和MCA增强了转化灶的发育。 CMCF的作用是模棱两可的，因为在更高的浓度下，CMCF实际上减少了MC诱导的灶的数量。包括该测定中的先前MX数据并考虑最低的活性浓度，病灶形成的起始活性按MX> CMCF> MCF的顺序降低，即随着4位甲基的氯原子数量减少CHF分子的原子数（分别为两个，一个和零）。相反，促销阶段的活动没有遵循相同的模式。 MX，MCF和MCA在相同浓度范围内均具有活性。因此，除了MX，MCF和MCA还可能具有促进肿瘤发展的潜力。

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