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

H.C.Blue 1在B6小鼠肝脏中是致癌的，但在F344大鼠中不致癌。 而H.C.Blue 2在这两个物种中都不会致癌。活体内 两种动物尿液中化学物质的代谢，以及体外 对两种动物肝细胞的代谢进行了分析。活体内 新陈代谢和肝细胞新陈代谢都给出了相似的高效液相图谱 化学药品。大鼠和小鼠在H.C.Blue 1中的数量差异 代谢产物的产生，这可能有助于H.C.蓝1‘S 物种专一性。特定代谢物的鉴定目前 被指认了。H.C.Blue 1对小鼠和大鼠DNA的加合作用 已对肝组织中有肝细胞进行了研究。但研究表明 表明杂质可能导致加合物的形成和 因此，对H.C.Blue 1进行了高效液相色谱纯化。从这些 研究，H.C.Blue 1中的一种导致突变和DNA的杂质 沙门氏菌中的内收作用已被分离。已经有七个DNA加合物被 在沙门氏菌中被确认。纯化的H.C.Blue 1没有致突变性， 而不是形成DNA加合物。研究仍在继续，试图阐明 H.C.蓝1‘S在小鼠体内致癌活性的基础及缺乏 大鼠体内的致癌活性。

H.C. Blue 1 is carcinogenic in the B6 mouse liver but not in the F344 rat, whereas H.C. Blue 2 is not carcinogenic in either species. The in vivo metabolism of the chemicals in the urine of both species, and the in vitro metabolism by hepatocytes from both species, have been analyzed. In vivo metabolism and hepatocyte metabolism gave similar HPLC profiles for each chemical. Rats and mice differed quantitatively in the H.C. Blue 1 metabolite profiles produced, which may contribute to the H.C. Blue 1's species specificity. The identity of specific metabolites are currently being identified. The adduction to DNA of H.C. Blue 1 to mouse and rat liver tissue had hepatocytes has been investigated. But studies have indicated an impurity(ies) may be responsible for adduct formation and therefore H.C. Blue 1 has been subjected to HPLC purification. From these studies, an impurity in H.C. Blue 1 responsible for mutagenicity and DNA adduction in Salmonella has been isolated. Seven DNA adducts have been identified in Salmonella. Purified H.C. Blue 1 is not mutagenic and does not form DNA adducts. Studies are continuing in an attempt to elucidate the basis of H.C. Blue 1's carcinogenic activity in the mouse and lack of carcinogenic activity in the rat.