Martelli A, Campart G B, Canonero R, Carrozzino R, Mattioli F, Robbiano L, Cavanna M
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, I-16132 Genoa, Italy.
Mutat Res. 1998 May 11;414(1-3):37-47. doi: 10.1016/s1383-5718(98)00037-0.
Auramine, a dye previously found to be a liver carcinogen in both mice and rats, was evaluated for its DNA-damaging and clastogenic activities in primary cultures of rats and human hepatocytes and for the induction of DNA single-strand breaks in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In contrast, neither rat nor human hepatocytes displayed an increased frequency of micronuclei after a 48-h exposure to the same auramine concentrations. In rats given a single oral dose of 125, 250 or 500 mg kg-1 auramine, the Comet assay revealed a significant increase in the frequency of DNA lesions in the liver and in the urinary bladder mucosa, the effect being slightly more marked in the liver. Taken as a whole and compared with previous findings, these results suggest that auramine is biotransformed into reactive species in target organs of both rats and humans, and that this dye might play by itself the main role in the increased incidence of bladder cancer which has been judged as causally related to its manufacture.
金胺是一种先前在小鼠和大鼠中均被发现为肝脏致癌物的染料，本研究评估了其在大鼠和人原代肝细胞中的DNA损伤和致断裂活性，以及在完整大鼠肝脏和膀胱黏膜中诱导DNA单链断裂的情况。在代谢活性良好的大鼠和人原代肝细胞中，采用碱性洗脱技术发现，暴露于10至32微摩尔亚毒性浓度的金胺20小时后，DNA片段化频率呈现相似的剂量依赖性。相比之下，在暴露于相同金胺浓度48小时后，大鼠和人原代肝细胞的微核频率均未增加。在单次口服125、250或500毫克/千克金胺的大鼠中，彗星试验显示肝脏和膀胱黏膜中DNA损伤频率显著增加，肝脏中的效应略为明显。总体而言，与先前的研究结果相比，这些结果表明金胺在大鼠和人类的靶器官中均被生物转化为反应性物质，并且这种染料本身可能在被判定与其制造有因果关系的膀胱癌发病率增加中起主要作用。
