Mechanism of 7,12-dimethylbenz[a]anthracene-induced immunotoxicity: role of metabolic activation at the target organ.

摘要: The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA), is an immunosuppressor as well a potent organ-specific carcinogen. To understand the mechanism of DMBA-induced lymphoid toxicity, aryl hydrocarbon-nonresponsive mice and microsomal epoxide hydrolase (mEH)-null were analyzed. DMBA caused dose-dependent decrease in spleen weights, but not thymus weights mice. On other hand, both decreased to less than half wild-type exposed 30 mg/kg DMBA. In contrast, no was detected mEH-null up 100 DMBA, while markedly lower. Responses B-cell mitogen lipopolysaccharide T-cell phytohemagglutinin nearly completely abolished splenocytes isolated from treated with These responses decreased, maintained Two metabolites dependent on mEH including DMBA-3,4-diol HPLC chromatogram microsomes mice, those results suggest involvement splenic activation for immunotoxicity difference toxicity between thymus.