Metabolism of the carcinogen 1,2-dimethylhydrazine by isolated human colon microsomes and human colon tumor cells in culture.
Human colon microsomes catalyze the metabolism of the model colon carcinogen 1,2-dimethylhydrazine. Activity appears to be distributed in a gradient towards the lower end of the colon. Highest activities were observed for microsomes prepared from the descending segment of the colon with the transverse segment exhibiting lower activities, while the ascending segment showed the lowest rate of metabolism. Dimethylhydrazine metabolism in each segment is inhibited significantly by inhibitors of the cytochrome P-450-dependent mixed function oxidase system. Microsomes prepared from a human colon tumor cell also catalyze the metabolism of 1,2-dimethylhydrazine. Metabolic activity in the cell line can be induced two-fold by treatment of cells with phenobarbital and three-fold by treatment of the cells with phenobarbital plus hydrocortisone. These results show that human colon activates 1,2-dimethylhydrazine and suggest that the human colon may be capable of activating other carcinogens in situ.
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D012809:Colon, Sigmoid / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D004127:Dimethylhydrazines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008763:Methylhydrazines / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D006899:Mixed Function Oxygenases; D019813:1,2-Dimethylhydrazine; D006854:Hydrocortisone; D010634:Phenobarbital