Yokota H, Hoshino J, Yuasa A
Mutat Res. 1986 Dec;172(3):231-6. doi: 10.1016/0165-1218(86)90060-1.
The mutagenicity of benzo[a]pyrene (B[a]P) in the Ames test using liver S9 fraction prepared from rats pretreated with eugenol (4-allyl-2-methoxyphenol) was suppressed to a lower level than that obtained using liver S9 from untreated rats. There was a reverse correlation between the mutagenicity of B[a]P and the dose of eugenol administered to the animals. Similarly suppressed mutagenicity was observed when liver microsomes, instead of the S9 fraction, were used in the Ames test. The mutagenic activity of B[a]P and arylhydrocarbon hydroxylase (AHH) could not be inhibited by the direct addition of eugenol into the assay mixtures. In eugenol-treated microsomes, cytochrome P-450 content, AHH activity and total B[a]P hydroxylase activity were decreased to 81, 29 and 48% of the control values, respectively. The mutagenicity of B[a]P catalyzed by microsomes from rats fed ad libitum on a diet containing 5% eugenol in the Ames test was significantly decreased. AHH activity and total B[a]P hydroxylase activity were also decreased in these liver microsomes. These results indicate that the activation of B[a]P in rat liver by cytochrome P-450, which metabolizes B[a]P to ultimate mutagens or carcinogens, is reduced by the administration of eugenol.
在艾姆斯试验中,使用经丁香酚(4-烯丙基-2-甲氧基苯酚)预处理的大鼠制备的肝脏S9组分时,苯并[a]芘(B[a]P)的致突变性被抑制到比使用未处理大鼠的肝脏S9时更低的水平。B[a]P的致突变性与给予动物的丁香酚剂量之间存在负相关。当在艾姆斯试验中使用肝微粒体而非S9组分时,也观察到了类似的致突变性抑制。将丁香酚直接添加到测定混合物中并不能抑制B[a]P和芳烃羟化酶(AHH)的致突变活性。在经丁香酚处理的微粒体中,细胞色素P-450含量、AHH活性和总B[a]P羟化酶活性分别降至对照值的81%、29%和48%。在艾姆斯试验中,用含5%丁香酚的饮食随意喂养的大鼠的微粒体催化的B[a]P致突变性显著降低。这些肝脏微粒体中的AHH活性和总B[a]P羟化酶活性也降低。这些结果表明,给予丁香酚可降低细胞色素P-450对大鼠肝脏中B[a]P的激活作用,细胞色素P-450可将B[a]P代谢为最终的诱变剂或致癌物。