Norppa H, Tursi F, Pfäffli P, Mäki-Paakkanen J, Järventaus H
Cancer Res. 1985 Oct;45(10):4816-21.
A 48-h treatment with vinyl acetate (0.05-1 mM) induced a drastic increase in sister chromatid exchanges (SCEs) and (in first division cells) structural chromosome aberrations in cultured human lymphocytes. The effects were more pronounced in cultures of isolated lymphocytes than in whole-blood cultures. A distinct dose-dependent induction of SCEs similarly occurred in Chinese hamster ovary cells after a 24-h vinyl acetate treatment (0.125-1 mM). A pulse treatment of Chinese hamster ovary cells for 4 h also yielded a clear increase in SCEs, but at higher concentrations (0.3-5 mM). The presence of rat liver S9 mix enhanced the SCE-inducing effect of vinyl acetate in Chinese hamster ovary cells. Gas chromatographic analysis of human whole-blood lymphocyte cultures treated for 10 s-20 min with vinyl acetate (5.4 mM) revealed a rapid degradation of vinyl acetate and formation of acetaldehyde. During the 20-min observation period, no degradation of vinyl acetate or formation of acetaldehyde were observed in complete culture medium without blood, which suggested that the reaction was enzymatic. Acetaldehyde induced SCEs in human whole-blood lymphocyte cultures at concentrations (0.125-2 mM) comparable to those used for vinyl acetate. The results indicate that vinyl acetate induces chromosome damage in cell cultures through enzyme-mediated hydrolysis to acetaldehyde.
用乙酸乙烯酯(0.05 - 1 mM)处理48小时可使培养的人淋巴细胞中的姐妹染色单体交换(SCEs)急剧增加,并(在第一次分裂细胞中)导致染色体结构畸变。这些效应在分离淋巴细胞培养物中比在全血培养物中更明显。用乙酸乙烯酯(0.125 - 1 mM)处理24小时后,中国仓鼠卵巢细胞中也同样出现了明显的剂量依赖性SCE诱导。对中国仓鼠卵巢细胞进行4小时的脉冲处理也使SCE明显增加,但浓度更高(0.3 - 5 mM)。大鼠肝脏S9混合物的存在增强了乙酸乙烯酯对中国仓鼠卵巢细胞的SCE诱导作用。对用乙酸乙烯酯(5.4 mM)处理10秒至20分钟的人全血淋巴细胞培养物进行气相色谱分析,结果显示乙酸乙烯酯迅速降解并形成乙醛。在20分钟的观察期内,在无血液的完全培养基中未观察到乙酸乙烯酯的降解或乙醛的形成,这表明该反应是酶促反应。乙醛在人全血淋巴细胞培养物中以与乙酸乙烯酯相当的浓度(0.125 - 2 mM)诱导SCE。结果表明,乙酸乙烯酯通过酶介导水解为乙醛而在细胞培养物中诱导染色体损伤。