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

已有研究阐明H.C.蓝1‘S致癌活性的基础 继续。H.C.Blue 1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.Blue 2不是 在这两个物种中都有致癌作用。在这一年，我们证明了 H.C.Blue 1中的杂质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1‘S致癌的原因 活动。用[14C]-甲基和环标记的H.C.进行代谢研究 蓝1和标有H.C.蓝2的[14C]-环已与B6进行了反应 小鼠和B6小鼠的肝细胞。研究表明， 去甲基化是致癌物H.C.Blue 1的主要途径，而 氧化为酸是主要的代谢途径(超过90%) H.C.Blue 2.代谢途径的这种差异如何有助于 不同的致癌活性，以及纯化的H.C.Blue 1是否可以 在肝脏或体外肝细胞中形成DNA加合物是人们追求的目标。

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.