Functional role of cytochrome p-450 2a3 in N-nitrosomethylbenzylamine metabolism in rat esophagus.

摘要: Previous in vitro studies demonstrated that the rat esophageal carcinogen N-nitrosomethylbenzylamine (NMBA) is metabolically activated by cytochrome P-450s (CYP) 2A3 and 2E1. However, vivo role of these metabolism NMBA has not been fully evaluated. In this study, effects single multiple doses were investigated on CYP2A3 CYP2E1 mRNA expression esophagus lung. Seven- to 8-wk old male Fischer 344 rats administered a subcutaneous dose at either 0.5 mg/kg or 2 body weight, after which sacrificed 1, 3, 6, 12, 24, 48, 72 h. multiple-dose experiment, groups dosed with weight 3 times per week for 1 wk wk. The animals 24 h following last treatment. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis reduction lung from NMBA-treated compared dimethyl sulfoxide (DMSO)-treated vehicle controls. This was significant 48 NMBA. contrast, remained unchanged treatment no consistent pattern could be observed esophagus. 32% 25% wk, respectively. Similar reductions also Further, explants derived pretreated reduced ability metabolize as control animals. Taken together, data provide further support potential Data suggest levels can determinant its vivo.