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2-乙酰氨基芴(2AAF)暴露小鼠肝脏中DNA的32P后标记与放射自显影UDS试验的相对敏感性

Relative sensitivity of 32P-postlabelling of DNA and the autoradiographic UDS assay in the liver of mice exposed to 2-acetylaminofluorene (2AAF).

作者信息

Ashby J, Lefevre P A, Shank T, Lewtas J, Gallagher J E

机构信息

ICI Central Toxicology Laboratory, Macclesfield, Cheshire, Great Britain.

出版信息

Mutat Res. 1991 Jun;252(3):259-68. doi: 10.1016/0165-1161(91)90005-s.

Abstract

In contrast to earlier studies conducted at lower dose levels, 2AAF is shown to induce a positive UDS response in the liver of mice dosed orally at dose levels between 500 and 1000 mg/kg. Similarly exposed mice had low levels of 2AAF-related hepatic DNA adducts at dose levels in the range 10-1000 mg/kg 2AAF, as determined by 32P-postlabelling analysis. It is concluded that the attenuated UDS response observed in the mouse liver, as compared to the rat liver, is due primarily to metabolic differences between these two species, coupled to a reduced capacity for UDS in the mouse liver for a given level of total 2AAF-related adducts per unit of DNA. These observations are compared and contrasted with identical studies conducted in the rat and reported in the preceding paper (Gallagher et al., 1991).

摘要

与早期在较低剂量水平进行的研究相比,2-乙酰氨基芴(2AAF)在口服剂量为500至1000mg/kg的小鼠肝脏中可诱导阳性的未计划DNA合成(UDS)反应。通过32P后标记分析确定,在10-1000mg/kg 2AAF剂量范围内,同样暴露的小鼠肝脏中2AAF相关的肝DNA加合物水平较低。得出的结论是,与大鼠肝脏相比,在小鼠肝脏中观察到的UDS反应减弱主要是由于这两个物种之间的代谢差异,再加上对于每单位DNA给定水平的总2AAF相关加合物,小鼠肝脏中UDS的能力降低。将这些观察结果与在前一篇论文(Gallagher等人,1991年)中报道的在大鼠中进行的相同研究进行了比较和对比。

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