Bastlová T, Vodicka P, Peterková K, Hemminki K, Lambert B
Center for Nutrition and Toxicology, Karolinska Institute, Huddinge, Sweden.
Carcinogenesis. 1995 Oct;16(10):2357-62. doi: 10.1093/carcin/16.10.2357.
Styrene-7,8-oxide (SO) is the major in vivo metabolite of styrene, a widely used plastic monomer. SO has been classified as probably carcinogenic to humans. We studied the genotoxic effects of SO in human peripheral blood lymphocytes (PBL) in vitro. SO-treatment in the range of 0.05-0.6 mM for 24 h resulted in a dose-dependent decrease of cell survival and increase of HPRT mutation, O6-guanine DNA adducts and DNA strand breaks, whereas higher concentrations caused pronounced cell death. SO was a weak mutagen, inducing at most 10-20 mutants per 10(6) clonable cells (approximately 4-fold over the background) after treatment with 0.2-0.4 mM for 24 h or 6 days. The levels of DNA adducts in treated cells correlated with SO-concentrations, but only four adducts per 10(8) nucleotides were detected at the highest treatment concentrations. Yet, adducts were still detectable in cells that had been cultured for 6-8 days after treatment. SO-induced DNA strand breaks, measured with the Comet assay, were detectable after 1 h exposure to 0.05-0.1 mM. Post-treatment incubation for 24 h decreased the level of DNA strand breaks to the control level. There was no correlation between the levels of DNA adducts and frequency of HPRT mutation. The present results indicate that SO is relatively inefficient in inducing HPRT mutation and O6-guanine DNA adducts in human lymphocytes in vitro, which may be related to its pronounced cytotoxicity at concentrations above 0.4 mM. A comparison with previous in vivo data obtained by the same assays in T-lymphocytes of styrene-exposed workers suggests that chronic, low dose exposure to styrene in the work environment may be more efficient in inducing persistent DNA adducts and HPRT mutation than acute, short-term exposure.
苯乙烯 -7,8 - 氧化物（SO）是苯乙烯在体内的主要代谢产物，苯乙烯是一种广泛使用的塑料单体。SO已被归类为对人类可能致癌。我们在体外研究了SO对人外周血淋巴细胞（PBL）的遗传毒性作用。0.05 - 0.6 mM浓度范围的SO处理24小时导致细胞存活率呈剂量依赖性下降，同时次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）突变、O6 - 鸟嘌呤DNA加合物和DNA链断裂增加，而更高浓度则导致明显的细胞死亡。SO是一种弱诱变剂，在用0.2 - 0.4 mM处理24小时或6天后，每10^6个可克隆细胞中最多诱导10 - 20个突变体（比背景值高约4倍）。处理后细胞中的DNA加合物水平与SO浓度相关，但在最高处理浓度下每10^8个核苷酸仅检测到4个加合物。然而，在处理后培养6 - 8天的细胞中仍可检测到加合物。用彗星试验测量，暴露于0.05 - 0.1 mM的SO 1小时后可检测到DNA链断裂。处理后孵育24小时使DNA链断裂水平降至对照水平。DNA加合物水平与HPRT突变频率之间没有相关性。目前的结果表明，SO在体外诱导人淋巴细胞中HPRT突变和O6 - 鸟嘌呤DNA加合物的效率相对较低，这可能与其在高于0.4 mM浓度时明显的细胞毒性有关。与先前在接触苯乙烯工人的T淋巴细胞中通过相同试验获得的体内数据进行比较表明，工作环境中慢性、低剂量接触苯乙烯可能比急性、短期接触更有效地诱导持续性DNA加合物和HPRT突变。
