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基因毒性致癌物在小鼠肝肿瘤中诱导小卫星DNA重排

Induction of minisatellite DNA rearrangements by genotoxic carcinogens in mouse liver tumors.

作者信息

Ledwith B J, Joslyn D J, Troilo P, Leander K R, Clair J H, Soper K A, Manam S, Prahalada S, van Zwieten M J, Nichols W W

机构信息

Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA.

出版信息

Carcinogenesis. 1995 May;16(5):1167-72. doi: 10.1093/carcin/16.5.1167.

Abstract

We investigated whether somatic rearrangements in minisatellite DNA are more frequent in chemically induced mouse liver tumors than they are in spontaneous tumors. CD-1 mouse liver tumors were induced by either a single dose or 15 consecutive daily doses of 7,12-dimethylbenz[alpha]anthracene, 4-aminoazobenzene, N-hydroxy-2-acetyl-aminofluorene or diethylnitrosoamine (DEN). Using DNA fingerprinting analysis, we found that the single- and multiple-dose carcinogen treatments caused a 2- to 5-fold higher frequency of minisatellite DNA rearrangements compared with that found in spontaneous tumors--with the exception of single-dose DEN tumors, which showed no increase in rearrangements. Our results suggest that DNA fingerprinting may be a valuable assay for differentiating certain chemically induced tumors from spontaneous tumors.

摘要

我们研究了在化学诱导的小鼠肝肿瘤中,小卫星DNA的体细胞重排是否比自发肿瘤中更频繁。用单次剂量或连续15天每天一次剂量的7,12-二甲基苯并[a]蒽、4-氨基偶氮苯、N-羟基-2-乙酰氨基芴或二乙基亚硝胺(DEN)诱导CD-1小鼠肝肿瘤。通过DNA指纹分析,我们发现与自发肿瘤相比,单次和多次剂量致癌物处理导致小卫星DNA重排频率高出2至5倍——单剂量DEN肿瘤除外,其重排未增加。我们的结果表明,DNA指纹分析可能是区分某些化学诱导肿瘤与自发肿瘤的有价值检测方法。

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