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致癌物铬酸盐会导致DNA损伤,并抑制药物介导的雏鸡胚胎肝细胞中卟啉积累和葡萄糖醛酸化的诱导。

The carcinogen chromate causes DNA damage and inhibits drug-mediated induction of porphyrin accumulation and glucuronidation in chick embryo hepatocytes.

作者信息

Tsapakos M J, Hampton T H, Sinclair P R, Sinclair J F, Bement W J, Wetterhahn K E

出版信息

Carcinogenesis. 1983 Aug;4(8):959-66. doi: 10.1093/carcin/4.8.959.

DOI:10.1093/carcin/4.8.959
PMID:6872154
Abstract

DNA damage by chromate in chick embryo hepatocytes has been correlated with the effect of chromate on inducible cell functions. Treatment of chick embryo hepatocytes with chromium(VI) in the form of sodium chromate resulted in the rapid uptake of chromate and the induction of DNA lesions in a time- and concentration-dependent manner. DNA interstrand cross-links, strand breaks and DNA-protein crosslinks, as measured by the alkaline elution technique, were observed after treatment of the hepatocytes with chromate concentrations (2.5- 0 microM) which did not affect cell viability. The effect of chromate on inducible cell functions was measured by assaying propylisopropylacetamide-induced accumulation of porphyrin and glucuronidation of phenol red by intact cells. Chromate inhibited propylisopropylacetamide-induction of porphyrin accumulation and phenol red glucuronidation in a time- and concentration-dependent manner which paralleled DNA damage. DNA damage was removed and inducibility of porphyrin accumulation by propylisopropylacetamide plus deferoxamine methanesulfonate was restored 21 h following a 2 h pretreatment with chromate. Chromium(III) in the form of chromic nitrate at concentrations up to 25 times those used with chromate had no effect on DNA damage or the induction of porphyrin accumulation and phenol red glucuronidation by propylisopropylacetamide in the cultured chick hepatocytes.

摘要

鸡胚肝细胞中铬酸盐造成的DNA损伤已与铬酸盐对诱导性细胞功能的影响相关联。用铬酸钠形式的铬(VI)处理鸡胚肝细胞,导致铬酸盐快速摄取,并以时间和浓度依赖性方式诱导DNA损伤。在用不影响细胞活力的铬酸盐浓度(2.5 - 0微摩尔)处理肝细胞后,通过碱性洗脱技术检测到DNA链间交联、链断裂和DNA - 蛋白质交联。通过测定完整细胞中丙基异丙基乙酰胺诱导的卟啉积累和酚红葡萄糖醛酸化来测量铬酸盐对诱导性细胞功能的影响。铬酸盐以时间和浓度依赖性方式抑制丙基异丙基乙酰胺诱导的卟啉积累和酚红葡萄糖醛酸化,这与DNA损伤情况平行。在用铬酸盐预处理2小时后21小时,DNA损伤消除,丙基异丙基乙酰胺加去铁胺甲磺酸盐诱导的卟啉积累恢复。在培养的鸡肝细胞中,浓度高达铬酸盐使用浓度25倍的硝酸铬形式的铬(III)对DNA损伤或丙基异丙基乙酰胺诱导的卟啉积累和酚红葡萄糖醛酸化没有影响。

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1
The carcinogen chromate causes DNA damage and inhibits drug-mediated induction of porphyrin accumulation and glucuronidation in chick embryo hepatocytes.致癌物铬酸盐会导致DNA损伤,并抑制药物介导的雏鸡胚胎肝细胞中卟啉积累和葡萄糖醛酸化的诱导。
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2
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