Degawa M, Yamaya C, Hashimoto Y
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Carcinogenesis. 1988 Apr;9(4):567-71. doi: 10.1093/carcin/9.4.567.
DBA/2, BALB/c or (BALB/c X DBA/2)F1 (CDF1) mice of both sexes were treated for 1 week with a dietary hepatocarcinogenic tryptophan pyrolysate component (Trp P-1 or Trp P-2), and the activity of hepatic microsomal enzyme(s) for mutagenic activations of Trp P-1 and Trp P-2 were assessed by means of a mutation test with Salmonella typhimurium TA98. In both Ah-responsive (BALB/c and CDF1) and Ah-nonresponsive (DBA/2) mice, the dietary treatment with Trp P-1 or Trp P-2 resulted in a significant increase of the enzyme activity for mutagenic activations of Trp P-1 and Trp P-2 in females but not in males, except the case of male BALB/c mice treated with dietary Trp P-1. Also induction of enzyme(s) in female mice was suppressed by an administration of testosterone. The induced hepatic microsomal enzyme(s) was demonstrated to be cytochrome P-450 isozyme(s) (mol. wt of 55,000 daltons) by immunoblots with use of an anti-rat cytochrome P-448 monoclonal antibody and by selective inhibition of the activity by addition of 7,8-benzoflavone into the mutation assay system. These findings indicate that carcinogenic aromatic amines such as Trp P-1 and Trp P-2 are able to induce hepatic cytochrome P-450 isozyme(s) not only in Ah-responsive mice (BALB/c and CDF1) but also in Ah-nonresponsive DBA/2 mice and that the cytochrome P-450 induction is controlled by androgen(s).
对不同性别的DBA/2、BALB/c或（BALB/c×DBA/2）F1（CDF1）小鼠，用一种具有肝癌致癌性的色氨酸热解产物成分（Trp P-1或Trp P-2）进行为期1周的饮食处理，通过鼠伤寒沙门氏菌TA98突变试验评估肝脏微粒体酶对Trp P-1和Trp P-2诱变激活的活性。在Ah反应型（BALB/c和CDF1）和Ah无反应型（DBA/2）小鼠中，用Trp P-1或Trp P-2进行饮食处理后，雌性小鼠中Trp P-1和Trp P-2诱变激活的酶活性显著增加，而雄性小鼠中除了用饮食Trp P-1处理的雄性BALB/c小鼠外，酶活性未增加。此外，给雌性小鼠注射睾酮可抑制酶的诱导。通过使用抗大鼠细胞色素P-448单克隆抗体进行免疫印迹以及在突变检测系统中添加7,8-苯并黄酮选择性抑制活性，证明诱导的肝脏微粒体酶是细胞色素P-450同工酶（分子量为55,000道尔顿）。这些发现表明，致癌芳香胺如Trp P-1和Trp P-2不仅能够在Ah反应型小鼠（BALB/c和CDF1）中诱导肝脏细胞色素P-450同工酶，而且能够在Ah无反应型DBA/2小鼠中诱导，并且细胞色素P-450的诱导受雄激素控制。
