COMPARATIVE GENETIC TOXICOLOGY OF H.C. BLUE 1 AND H.C. BLUE 2

研究以阐明H.C.蓝色1的致癌活性 持续期间内的 H.C.蓝1号在36只小鼠的肝脏中是致癌的，但在 F344大鼠，而结构类似物H.C.蓝色2号，不是 在任何物种中都是致癌的。 在这一年里，我们已经证明， H.C.中的杂质 蓝1号是其沙门氏菌致突变性的原因， 和DNA内收。 因此，越来越多的证据表明， 非遗传毒性机制可能是H.C.蓝色1号是致癌的 活动 使用[14 C]-甲基和环标记的H.C.进行代谢研究。 蓝色1和[14 C]-环标记的H. C. 蓝色2已使用B6进行 小鼠和来自B6小鼠的肝细胞。 研究表明， 去甲基化是致癌物HC的主要途径。蓝色1，而 氧化为酸是主要的代谢途径（大于90%）， H.C.蓝色2号 代谢途径的这种差异如何导致 不同的致癌活性，以及纯化的H.C.蓝色1罐 形成DNA加合物在肝脏或肝细胞在体外正在追求。

Studies to elucidate the basis of H.C. Blue 1's carcinogenic activity have continued. H.C. Blue 1 is carcinogenic in the 36 mouse liver, but not in the F344 rat, whereas the structural analogue, H.C. Blue 2, is not carcinogenic in either species. During this year we have demonstrated that impurities in H.C. Blue 1 are responsible for its Salmonella mutagenicity, and DNA adduction. Thus, evidence is accumulating to indicate that a nongenotoxic mechanism may account for H.C. Blue 1's carcinogenic activities. Metabolic studies using [14C]-methy- and ring-labeled H.C. Blue 1, and [14C]-ring labeled H.C. Blue 2 have been conducted with B6 mice and hepatocytes from the B6 mouse. The studies have indicated that demethylation is a major pathway for the carcinogen, H.C. Blue 1, whereas oxidation to an acid is the major metabolic pathway (greater than 90%) for H.C. Blue 2. How this difference in metabolic pathways could contribute to differing carcinogenic activities, and whether purified H.C. Blue 1 can form DNA adducts in the liver or hepatocytes in vitro are being pursued.