Induction and suppression of N-nitrosomethylbenzylamine activation by microsomes from rat liver and esophagus.
Male Sprague-Dawley rats were pretreated with various chemicals to determine their effects on the microsomal activation of the esophageal carcinogen N-nitrosomethylbenzylamine [( NMBzA ) CAS: 937-40-6; N-methyl-N- nitrosobenzylamine ] in the rat esophagus and, for comparative purposes, in the rat liver. When rats were pretreated with NMBzA , little change in hepatic NMBzA - debenzylase activity was observed. In contrast, NMBzA metabolism in the esophagus was significantly (60-65%) reduced. Similarly, pretreatment of rats with disulfiram [CAS: 97-77-8; bis( diethylthiocarbamoyl )disulfide] caused a 40% decrease in esophageal metabolism, but it had no significant effect in the liver. Pretreatments with the methylenedioxybenzenes safrole [CAS: 94-59-7; 4-allyl-1,2-(methylenedioxy)benzene], isosafrole [CAS: 120-58-1; 1,2-(methylenedioxy)-4-propenylbenzene], and dihydrosafrole (CAS: 94-58-6; 1,2-(methylenedioxy)-4- propylbenzene ) caused a marked induction (twofold to fivefold) of the hepatic metabolism of NMBzA , but again esophageal metabolism was suppressed. The results indicate that esophageal metabolism of NMBzA is either unchanged or suppressed by the various chemical pretreatments, but hepatic metabolism of the nitrosamine is induced by the methylenedioxybenzenes .
D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D007928:Lethal Dose 50; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System; C014707:nitrosobenzylmethylamine; D010088:Oxidoreductases; C041729:N-nitrosomethylbenzylamine debenzylase; D004128:Dimethylnitrosamine