Stenius U, Warholm M, Högberg J
Department of Toxicology, National Institute of Occupational Health, Solna, Sweden.
Cancer Lett. 1993 Feb;68(2-3):149-57. doi: 10.1016/0304-3835(93)90141-u.
In this paper data is presented suggesting selective toxicity towards enzyme altered hepatocytes. Hydroquinone (HQ) treatment 24 or 48 h after diethylnitrosamine (DEN) initiation reduced the number of glutathione S-transferase-P (GST-P)-positive hepatocytes in situ. Furthermore, in experiments on primary cultures of hepatocytes from control rats a synergism in cell killing between DEN and HQ was observed. In another in vitro system the effect of HQ and duroquinone (DQ) on GGT-positive and -negative hepatocytes was investigated. DQ was shown to affect the GGT-positive cells, while HQ mainly affected GGT-negative cells. These results suggest that HQ can reduce the population of enzyme altered foci (EAF) precursor cells by synergistic interactions with DEN, but provide no support for the notion that HQ selectively damage cells in developed EAF. This conclusion is supported by previously published data on effects of HQ on the development of EAF.
本文呈现的数据表明对酶改变的肝细胞具有选择性毒性。在二乙基亚硝胺(DEN)启动后24或48小时进行对苯二酚(HQ)处理,可原位减少谷胱甘肽S-转移酶-P(GST-P)阳性肝细胞的数量。此外,在对对照大鼠肝细胞原代培养的实验中,观察到DEN和HQ之间在细胞杀伤方面存在协同作用。在另一个体外系统中,研究了HQ和杜醌(DQ)对γ-谷氨酰转肽酶(GGT)阳性和阴性肝细胞的影响。结果表明DQ影响GGT阳性细胞,而HQ主要影响GGT阴性细胞。这些结果表明,HQ可通过与DEN的协同相互作用减少酶改变灶(EAF)前体细胞的数量,但并不支持HQ选择性损伤已形成的EAF中细胞这一观点。先前发表的关于HQ对EAF发展影响的数据支持了这一结论。