Martelli A, Robbiano L, Carrozzino R, Puglia C P, Mattioli F, Angiola M, Brambilla G
Department of Internal Medicine, University of Genoa, Italy.
Toxicol Sci. 2000 Jan;53(1):71-6. doi: 10.1093/toxsci/53.1.71.
3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye industry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder mucosa of intact rats. A similar modest 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 DMB concentrations ranging from 56 to 180 microM. Replicating rat hepatocytes displayed a modest increase in the frequency of micronucleated cells after a 48-h exposure to 100 and 180 microM concentrations. In primary cultures of human urinary bladder mucosa cells exposed for 20 h to 100 and 180 microM DMB, the Comet assay revealed a clear-cut increase of DNA fragmentation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, these results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary bladder might be the consequence of pharmacokinetic behavior.
3,3'-二甲氧基联苯胺（DMB）是一种用于染料工业的联苯胺同系物，此前已发现其对大鼠具有致癌性。本研究对其在大鼠和人原代肝细胞、人膀胱黏膜细胞以及完整大鼠的肝脏和膀胱黏膜中的遗传毒性活性进行了评估。采用碱性洗脱技术，在代谢功能正常的大鼠和人原代肝细胞中，将其暴露于56至180微摩尔/升的亚毒性DMB浓度下20小时，发现DNA片段化频率呈适度剂量依赖性增加。在复制的大鼠肝细胞中，暴露于100和180微摩尔/升浓度48小时后，微核细胞频率有适度增加。在人膀胱黏膜细胞原代培养物中，暴露于100和180微摩尔/升DMB 20小时后，彗星试验显示DNA片段化明显增加。给大鼠单次口服一半LD50的DMB后，肝脏和膀胱黏膜中的谷胱甘肽水平均降低，而仅在膀胱黏膜中检测到DNA片段化。总体而言，这些结果表明，DMB在大鼠和人类中均应被视为潜在的遗传毒性化学物质；对大鼠膀胱的选择性作用可能是药代动力学行为的结果。
