环氧丙烷和环氧氯丙烷可诱导人类二倍体成纤维细胞中的DNA链断裂。

Propylene oxide and epichlorohydrin induce DNA strand breaks in human diploid fibroblasts.

作者信息

Kolman A, Spivak I, Näslund M, Dusinská M, Cedervall B

机构信息

Department of Radiobiology, Stockholm University, Sweden.

出版信息

Environ Mol Mutagen. 1997;30(1):40-6. doi: 10.1002/(sici)1098-2280(1997)30:1<40::aid-em6>3.0.co;2-g.

DOI:10.1002/(sici)1098-2280(1997)30:1<40::aid-em6>3.0.co;2-g

PMID:9258328

Abstract

The induction of DNA strand breaks in human diploid fibroblasts (VH-10) was demonstrated after in vitro exposure with two carcinogenic epoxides, propylene oxide (PO) and epichlorohydrin (ECH). Alkaline DNA unwinding (ADU), pulsed field gel electropharosis (PFGE), and the comet assay were used to measure DNA single. (SSBs) and double-strand breaks (DSBs). A dose-dependent increase of DNA strand breaks, measured by ADU, was observed in the dose range 2.5-20 mMh of PO and 0.25-2 mMh of ECH. The dose-response of ECH was about five times higher compared with that of PO (211 vs. 41 SSBs. 100 Mbp-1.mMh-1). The induction rates of DSBs, measured by PFGE, were found to be 18 times higher for ECH compared to PO (4.8 and 0.27 DSBs.100 Mbp-1.mMh-1 for ECH and PO, respectively). Using these two methods, the SSBs/ DSBs ratio was estimated to be 148 for PO and 44 for ECH. The data obtained by the comet assay also demonstrated a dose-dependent ability of PO and ECH to induce DNA damage. It was found that ECH was about six times more effective as an inducer of DNA strand breaks compared to PO (200 and 32x100 Mbp-1.mMh-1 for ECH and PO, respectively). The SSBs/DSBs ratios calculated using comet assay and PFGE data were 125 for ECH and 41 for PO. In addition, ECH is about 10 times more toxic than PO with respect to survival. These properties of ECH can at least in part be explained by its higher chemical reactivity connected with a higher rate of DNA alkylation.

摘要

在体外将人二倍体成纤维细胞（VH - 10）暴露于两种致癌环氧化合物环氧丙烷（PO）和环氧氯丙烷（ECH）后，证实了DNA链断裂的诱导。采用碱性DNA解旋（ADU）、脉冲场凝胶电泳（PFGE）和彗星试验来测量DNA单链（SSB）和双链断裂（DSB）。在PO浓度为2.5 - 20 mM·h和ECH浓度为0.25 - 2 mM·h的剂量范围内，通过ADU测量观察到DNA链断裂呈剂量依赖性增加。ECH的剂量反应比PO高约五倍（211对41个SSB·100 Mbp⁻¹·mM⁻¹·h⁻¹）。通过PFGE测量，发现ECH的DSB诱导率比PO高18倍（ECH和PO分别为4.8和0.27个DSB·100 Mbp⁻¹·mM⁻¹·h⁻¹）。使用这两种方法，PO的SSB/DSB比值估计为148，ECH为44。彗星试验获得的数据也证明了PO和ECH诱导DNA损伤的剂量依赖性能力。发现ECH作为DNA链断裂诱导剂比PO有效约六倍（ECH和PO分别为200和32×100 Mbp⁻¹·mM⁻¹·h⁻¹）。使用彗星试验和PFGE数据计算的SSB/DSB比值，ECH为125，PO为41。此外，就细胞存活而言，ECH的毒性比PO高约10倍。ECH的这些特性至少部分可以由其与更高的DNA烷基化速率相关的更高化学反应性来解释。