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丙烯酰胺;诱导DNA损伤、染色体畸变以及细胞转化但不发生基因突变。

Acrylamide; induction of DNA damage, chromosomal aberrations and cell transformation without gene mutations.

作者信息

Tsuda H, Shimizu C S, Taketomi M K, Hasegawa M M, Hamada A, Kawata K M, Inui N

机构信息

Life Science Research Laboratory, Japan Tobacco Inc., Kanagawa.

出版信息

Mutagenesis. 1993 Jan;8(1):23-9. doi: 10.1093/mutage/8.1.23.

Abstract

The genotoxic potential of acrylamide monomer (AA), a compound familiar as a raw material of polyacrylamide electrophoresis gel, was extensively investigated in vitro. The results were clear cut: AA did not induce any gene mutations in Salmonella/microsome test systems (TA98, TA100, TA1535, TA1537), Escherichia coli/microsome assay (WP2 uvrA-) up to a dose of 50 mg AA/plate, or in HPRT-locus in Chinese hamster V79H3 cells (AA, 1-7 mM, 24 h treatment). On the other hand, AA showed a strong positive response: (a) in a Bacillus subtilis spore-rec assay (DNA damage) at 10-50 mg/disc, (b) to a chromosomal structural change test (AA, 2-5 mM, 24 h treatment), (c) to a polyploidy test (AA, 1-5 mM, 24 h treatment) in Chinese hamster V79H3 cells, (d) to a cell transformation assay in mouse BALB/c3T3 cells (AA, 1-2 mM, 72 h treatment). Sister chromatid exchange was also weakly but significantly induced by AA (AA, 1-2.5 mM, 24 h treatment) in Chinese hamster V79H3 cells. Carcinogenic potential of AA was reported in mice and rats several years ago. AA thus seems to be a typical clastogenic rodent carcinogen without any gene mutation potential. Furthermore, this experiment showed for the first time positive response of AA to a microbial test system (B. subtilis spore-rec assay).

摘要

丙烯酰胺单体(AA)作为聚丙烯酰胺电泳凝胶的一种原材料为人所熟知,其遗传毒性潜力在体外得到了广泛研究。结果很明确:在高达50毫克AA/平板的剂量下,AA在沙门氏菌/微粒体测试系统(TA98、TA100、TA1535、TA1537)、大肠杆菌/微粒体试验(WP2 uvrA-)中未诱导任何基因突变,在中国仓鼠V79H3细胞的次黄嘌呤磷酸核糖转移酶基因座(AA,1 - 7毫摩尔,处理24小时)中也未诱导基因突变。另一方面,AA显示出强烈的阳性反应:(a)在枯草芽孢杆菌孢子回复试验(DNA损伤)中,剂量为10 - 50毫克/圆片;(b)在染色体结构变化试验中(AA,2 - 5毫摩尔,处理24小时);(c)在中国仓鼠V79H3细胞的多倍体试验中(AA,1 - 5毫摩尔,处理24小时);(d)在小鼠BALB/c3T3细胞的细胞转化试验中(AA,1 - 2毫摩尔,处理72小时)。在中国仓鼠V79H3细胞中,AA(AA,1 - 2.5毫摩尔,处理24小时)也能微弱但显著地诱导姐妹染色单体交换。几年前在小鼠和大鼠中报道了AA的致癌潜力。因此,AA似乎是一种典型的致染色体断裂的啮齿动物致癌物,没有任何基因突变潜力。此外,该实验首次显示了AA对微生物测试系统(枯草芽孢杆菌孢子回复试验)的阳性反应。

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