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六价铬诱导的大鼠肾脏、肝脏和肺中的DNA损伤及铬分布。

Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung.

作者信息

Tsapakos M J, Hampton T H, Wetterhahn K E

出版信息

Cancer Res. 1983 Dec;43(12 Pt 1):5662-7.

PMID:6640521
Abstract

DNA lesions were detected in rat organ nuclei following an i.p. injection of sodium dichromate. Kidney, liver, and lung nuclei were examined for DNA interstrand cross-links, strand breaks, and DNA-protein cross-links using the alkaline elution technique. The time course for formation of cross-links in kidney nuclei revealed the presence of DNA interstrand and DNA-protein cross-links 1 hr after injection of sodium dichromate. By 40 hr in kidney, DNA interstrand cross-links had been repaired, but DNA-protein cross-links persisted. In liver nuclei, the time course for formation of cross-links after injection of dichromate showed a maximum in DNA-protein cross-linking at 4 hr and a maximum in DNA interstrand cross-linking at 2 hr. By 36 hr, in the liver, both types of lesions had been repaired. In lung nuclei, both DNA interstrand and DNA-protein cross-links were observed 1 hr after dichromate injection; however, by 36 hr, only DNA-protein cross-links persisted. No DNA lesions were detectable in kidney 1 hr after an i.p. injection of chromium(III) chloride. Chromium distribution in rat kidney, liver, and lung was measured and is discussed with respect to the observed DNA lesions. The lung and kidney may be more sensitive than liver to chromium-induced DNA damage, an observation which correlates with the reported toxicity and carcinogenicity data for chromium(VI) in both animals and humans.

摘要

腹腔注射重铬酸钠后,在大鼠器官细胞核中检测到DNA损伤。使用碱性洗脱技术,对肾脏、肝脏和肺细胞核进行DNA链间交联、链断裂和DNA-蛋白质交联检测。肾脏细胞核中交联形成的时间进程显示,注射重铬酸钠1小时后存在DNA链间交联和DNA-蛋白质交联。在肾脏中,到40小时时,DNA链间交联已修复,但DNA-蛋白质交联仍然存在。在肝脏细胞核中,注射重铬酸盐后交联形成的时间进程显示,DNA-蛋白质交联在4小时达到最大值,DNA链间交联在2小时达到最大值。在肝脏中,到36小时时,两种类型的损伤均已修复。在肺细胞核中,注射重铬酸盐1小时后观察到DNA链间交联和DNA-蛋白质交联;然而,到36小时时,仅DNA-蛋白质交联仍然存在。腹腔注射氯化铬(III)1小时后,在肾脏中未检测到DNA损伤。测定了铬在大鼠肾脏、肝脏和肺中的分布,并结合观察到的DNA损伤进行了讨论。肺和肾脏可能比肝脏对铬诱导的DNA损伤更敏感,这一观察结果与报道的铬(VI)在动物和人类中的毒性和致癌性数据相关。

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