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敌敌畏对小鼠皮肤微核的诱导作用

Micronuclei induction by dichlorvos in the mouse skin.

作者信息

Tungul A, Bonin A M, He S, Baker R S

机构信息

Toxicology Unit, National Institute of Occupational Health and Safety, Sydney, New South Wales, Australia.

出版信息

Mutagenesis. 1991 Sep;6(5):405-8. doi: 10.1093/mutage/6.5.405.

Abstract

Micronucleus (MN) induction in cultured keratinocytes was investigated following skin painting of HRA/Skh mice with the pesticide, dichlorvos. Whole skin and partially-purified epidermal cells from 5-6 week old male animals were cultured for 4 days in vitro after single topical applications of various concentrations of dichlorvos in vivo. Appropriate doses, allowing optimum survival of keratinocytes, were selected following an initial range-finding experiment. To evaluate MN induction in dividing cells, the cytokinesis-block method was employed. Results showed statistically significant MN at all dose levels in partially-purified epidermal cells and a positive trend with respect to dose from 51 to 1033 nmol dichlorvos. A significant increase in MN was also detectable in cultured cells from whole skin, dissociated within as little as 1 h after application of dichlorvos. Although a number of technical difficulties are associated with the skin micronucleus method, it has been used successfully in this laboratory to detect several skin carcinogens of both high and low potency. Since dichlorvos is rapidly absorbed through the skin, and can induce MN in skin cells of treated mice, this compound may therefore be considered to pose a contact hazard for exposed humans.

摘要

在用农药敌敌畏对HRA/Skh小鼠进行皮肤涂抹后,研究了培养的角质形成细胞中的微核(MN)诱导情况。在体内单次局部应用不同浓度的敌敌畏后,从5 - 6周龄雄性动物获取的全层皮肤和部分纯化的表皮细胞在体外培养4天。在最初的剂量范围探索实验后,选择了能使角质形成细胞实现最佳存活的合适剂量。为了评估分裂细胞中的MN诱导情况,采用了胞质分裂阻滞法。结果显示,在部分纯化的表皮细胞中,所有剂量水平下的MN均具有统计学意义,并且从51至1033纳摩尔敌敌畏,MN呈现出与剂量相关的正向趋势。在应用敌敌畏后仅1小时内解离的全层皮肤培养细胞中,也可检测到MN显著增加。尽管皮肤微核检测方法存在一些技术难题,但该方法已在本实验室成功用于检测多种高效和低效的皮肤致癌物。由于敌敌畏可通过皮肤迅速吸收,并能在处理过的小鼠皮肤细胞中诱导MN,因此该化合物可能对接触的人类构成接触危害。

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