Possible mechanism of Sudan III-induced prevention of chemical carcinogenesis in rats.
Possible mechanism of Sudan III-induced prevention of chemical carcinogenesis in rats.
复制标题
苏丹III诱导预防大鼠化学致癌的可能机制。
作者：
Shoichi Fujita;Takashi Matsunaga;Y. Masubuchi;Tokuji Suzuki
研究了用苏丹III处理大鼠对肝脏将苯并（a）芘（BP）转化为诱变剂的能力的影响，以阐明苏丹III诱导的预防化学致癌作用的可能机制（Huggins等人，Proc. Natl. Acad.科学，75：4524-4527，1978），使用改良的艾姆斯诱变测试系统。用常规艾姆斯法将BP与苏丹III处理的大鼠肝脏9000 x g上清液（S-9）预孵育，可显著增加BP的致突变性。回复突变菌落数的增加与所用S-9组分的芳烃羟化酶活性成比例（r大于0.9）。这种偶氮染料被发现诱导细胞色素P-448，这是一种前致癌物的活化酶和UDP葡糖醛酸转移酶和谷胱甘肽-S-转移酶（GST），这是活性致癌中间体的解毒酶的活动。抗细胞色素P-448抗体或UDP葡萄糖醛酸基转移酶和谷胱甘肽-S-转移酶的辅因子添加到肝脏S-9预孵育混合物与BP引起BP致突变性显着下降时，肝脏S-9馏分苏丹III治疗大鼠使用。通过添加辅因子获得的减少与UDP葡萄糖醛酸转移酶或谷胱甘肽-S-转移酶的诱导水平成比例。得出的结论是，苏丹III诱导的化学致癌作用的预防是由于加速消除的致癌物质的诱导细胞色素P-448和解毒酶与有限的增加水平的活性代谢中间体。
The effect of treatment of rats with Sudan III on the ability of the liver to transform benzo(a)pyrene (BP) to a mutagen was investigated to elucidate a possible mechanism of the Sudan III-induced prevention of chemical carcinogenesis (Huggins et al., Proc. Natl. Acad. Sci., 75:4524-4527, 1978) using a modified Ames mutagenesis test system. Preincubation of BP with liver 9000 x g supernatant (S-9) from rats treated with Sudan III markedly increased the mutagenicity of BP in the conventional Ames method. The increase in number of revertant colonies was proportional to the aryl hydrocarbon hydroxylase activity of the S-9 fractions used (r greater than 0.9). This azo dye was found to induce both cytochrome P-448 which is an activating enzyme of procarcinogens and the activities of UDP glucuronyl transferase and glutathione-S-transferase (GST), which are detoxifying enzymes of active carcinogenic intermediates. The addition of anti-cytochrome P-448 antibody or the cofactors for UDP glucuronyl transferase and glutathione-S-transferase to the liver S-9 preincubation mixture with BP caused a marked decrease in BP mutagenicity when liver S-9 fractions from Sudan III-treated rats were used. The decrease obtained by the addition of the cofactors was proportional to the induced levels of the UDP glucuronyl transferase or glutathione-S-transferase. It was concluded that Sudan III-induced prevention of chemical carcinogenesis is due to an accelerated elimination of the carcinogen by the induction of both cytochrome P-448 and detoxifying enzymes with a limited increase in levels of active metabolic intermediates.
苏丹Ⅲ对药物代谢酶的影响。
影响因子：
5.1
作者：
Fujita,S;Peisach,J;Ohkawa,H;Yoshida,Y;Adachi,S;Uesugi,T;Suzuki,M;Suzuki,T
通讯作者：
Suzuki,T