The carcinogen chromate causes DNA damage and inhibits drug-mediated induction of porphyrin accumulation and glucuronidation in chick embryo hepatocytes.
The carcinogen chromate causes DNA damage and inhibits drug-mediated induction of porphyrin accumulation and glucuronidation in chick embryo hepatocytes.
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致癌物质铬酸盐会造成 DNA 损伤，并抑制药物介导的鸡胚肝细胞中卟啉积累和葡萄糖醛酸化的诱导。
DOI：
10.1093/carcin/4.8.959
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发表时间：
1983
期刊：
影响因子：
4.7
通讯作者：
Wetterhahn,KE
中科院分区：
文献类型：
--
作者：
Tsapakos,MJ;Hampton,TH;Sinclair,PR;Sinclair,JF;Bement,WJ;Wetterhahn,KE
铬酸盐对鸡胚肝细胞DNA的损伤与铬酸盐对诱导细胞功能的影响有关。用铬酸钠形式的铬（VI）处理鸡胚肝细胞导致铬酸盐的快速摄取和以时间和浓度依赖性方式诱导DNA损伤。用不影响细胞活力的铬酸盐浓度（2.5-10μM）处理肝细胞后，观察到DNA链间交联、链断裂和DNA-蛋白质交联（通过碱性洗脱技术测量）。铬酸盐对诱导细胞功能的影响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葡萄糖醛酸化酚红来测量。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，从而抑制DNA损伤。DNA损伤被去除，并诱导卟啉积累的丙基异丙基乙酰胺加去铁胺甲烷磺酸盐恢复21小时后，2小时的铬酸盐预处理。铬（III）的形式，硝酸铬的浓度高达25倍，使用铬酸盐没有影响DNA损伤或诱导卟啉积累和酚红葡萄糖醛酸化的propylisopropylacetamide在培养的鸡肝细胞。
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 inter-strand cross-links, strand breaks and DNA-protein cross-links, as measured by the alkaline elution technique, were observed after treatment of the hepatocytes with chromate concentrations (2.5–10μM) 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 propylisopropyl-acetamide-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 methane-sulfonate 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 propyliso-propylacetamide in the cultured chick hepatocytes.