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致癌物可诱导人类细胞发生染色体内重组。

Carcinogens induce intrachromosomal recombination in human cells.

作者信息

Aubrecht J, Rugo R, Schiestl R H

机构信息

Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.

出版信息

Carcinogenesis. 1995 Nov;16(11):2841-6. doi: 10.1093/carcin/16.11.2841.

Abstract

A major portion of new cases of cancer may be linked to environmental carcinogens. The Ames (Salmonella) test is currently the most widely used short-term test to predict carcinogenic properties of compounds. However, approximately 50% of all carcinogens have been sufficiently tested in long-term animal bioassays do not induce mutations in the Salmonella assay, and many of these carcinogens are also not detectable by other short-term assays. In the work described here we determined the effect of carcinogen exposure on intrachromosomal recombination in a human cell line. The recombination events caused the deletion of one copy of a duplication of exons 2 and 3 of the hprt gene. We found that these deletion events were induced by exposure to the Salmonella assay positive carcinogens UV, gamma-rays and methyl methanesulfonate, as well as the Salmonella assay negative carcinogens Aroclor 1221, benzene and thiourea. These data may further support the accumulating evidence that recombination and deletions may be important in carcinogenesis.

摘要

大部分新增癌症病例可能与环境致癌物有关。艾姆斯(沙门氏菌)试验是目前预测化合物致癌特性应用最广泛的短期试验。然而,在长期动物生物测定中经过充分测试的所有致癌物中,约有50%在沙门氏菌试验中不会诱导突变,而且其中许多致癌物也无法通过其他短期试验检测到。在本文所述的研究中,我们确定了致癌物暴露对人细胞系中染色体内部重组的影响。这些重组事件导致hprt基因外显子2和3的一个重复拷贝缺失。我们发现,这些缺失事件是由暴露于沙门氏菌试验阳性致癌物紫外线、γ射线和甲磺酸甲酯,以及沙门氏菌试验阴性致癌物多氯联苯混合物1221、苯和硫脲诱导产生的。这些数据可能进一步支持越来越多的证据,即重组和缺失在致癌过程中可能很重要。

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