Pool B L, Brendler S Y, Liegibel U M, Tompa A, Schmezer P
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Environ Mol Mutagen. 1990;15(1):24-35. doi: 10.1002/em.2850150105.
This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.
本报告重点关注使用从大鼠不同组织和器官中新鲜分离的原代哺乳动物细胞，对有毒和基因毒性化学物质进行快速有效的分析。这些细胞要么在体外进行处理，要么从经处理的动物中分离出来。在这两种情况下，均通过台盼蓝排斥法监测细胞活力，并监测作为单链断裂的DNA损伤。因此，可以直接比较体外和体内的结果。使用源自三种物种（大鼠、仓鼠和猪）的肝细胞以及大鼠肺和肾细胞，在体外研究了具有独特器官特异性致癌模式的N-亚硝胺。尽管未观察到细胞特异性激活模式，但实现了对所有致癌性亚硝胺的灵敏检测。体内方法的新改进使得能够灵敏检测肝组织和肝外组织中的NDMA基因毒性。需要指出的是，该方法是体内对基因毒性致癌物进行毒代动力学研究的有效工具。
