Sandhu P, Chipman J K
School of Biochemistry, University of Birmingham, Great Britain.
Mutat Res. 1990 Mar;240(3):227-36. doi: 10.1016/0165-1218(90)90062-7.
5 azo dye components of Gurr chrysoidine 'Y' have been separated, synthesised and identified. Dyes with a methyl substitution (particularly between the two amino groups) were more mutagenic in Salmonella typhimurium strain TA100 with control rat liver S9 than the non-methylated counterpart (range 66-1992 revertants at 50 micrograms/plate). Mutagenicity was also catalysed by human-liver S9 and pre-treatment of rats with either phenobarbitone or beta-naphthoflavone enhanced the activation ability of S9 by greater than 4-fold. Using the most potent promutagenic component (2,4-diamino-3-methylazobenzene), the use of inhibitors of cytochrome P450 (metyrapone: 1.0 mM; alpha-naphthoflavone: 0.075 mM; DPEA: 0.125 mM) and of the flavin monooxygenase (methimazole: 0.75 mM) suggested a major role for cytochrome P448 in the activation of chrysoidine to mutagens. The ability of chrysoidine components to induce unscheduled DNA synthesis in rat hepatocytes in vitro was demonstrated and ranged between 11.92 and 23.5 net nuclear grains at a dose level of 2.5 micrograms/incubation. Since each dye was equi-potent, methyl substitution had little influence on genetic toxicity in hepatocytes.
已对格氏金橙黄“Y”的5种偶氮染料成分进行了分离、合成和鉴定。在带有对照大鼠肝脏S9的鼠伤寒沙门氏菌TA100菌株中，带有甲基取代基（特别是在两个氨基之间）的染料比未甲基化的对应物具有更强的致突变性（在50微克/平板时回复突变体范围为66 - 1992）。人肝脏S9也能催化致突变性，用苯巴比妥或β - 萘黄酮预处理大鼠可使S9的激活能力增强4倍以上。使用最有效的前诱变剂成分（2,4 - 二氨基 - 3 - 甲基偶氮苯），细胞色素P450抑制剂（甲吡酮：1.0 mM；α - 萘黄酮：0.075 mM；二苯乙胺：0.125 mM）和黄素单加氧酶抑制剂（甲巯咪唑：0.75 mM）的使用表明细胞色素P448在金橙黄激活为诱变剂过程中起主要作用。已证明金橙黄成分在体外诱导大鼠肝细胞非定标性DNA合成的能力，在剂量水平为2.5微克/培养时，净核颗粒数在11.92至23.5之间。由于每种染料效力相当，甲基取代对肝细胞中的遗传毒性影响很小。
