Comparison of metabolic activation of carcinogens in human, rat, and hamster hepatocytes.
The activities to activate and detoxify procarcinogens were compared in intact hepatocytes from humans, Sprague-Dawley rats and Syrian golden hamsters. Mutagenic metabolites that were released from the isolated hepatocytes were detected by mutation induction in co-cultivated Salmonella typhimurium TA98. Hepatocytes from the 3 animal species all activated aflatoxin B1 (AFB1), acetylaminofluorene (AAF) and aminofluorene (AF) and released active metabolites to induce mutation in the indicator S. typhimurium T98. Hamster hepatocytes were more effective than were human and rat hepatocytes to mediate mutation of Salmonella TA98 by AFB1, AAF and AF. Hepatocytes of human and rat failed to mediate mutation by 1-aminopyrene (1-AP). Indeed, at low concentration of 1-AP and 1-nitropyrene (1-NP), the presence of the hepatocytes decreased the number of TA98 revertants. Only at higher concentrations of 1-aminopyrene and 1-nitropyrene did hamster hepatocytes increase mutation frequencies of indicator cells over the control groups. It seems that hepatocytes, particularly human hepatocytes, are better able to absorb and detoxify 1-AP and 1-NP than to activate them.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism; D051381:Rats
D000348:Aflatoxins; D002273:Carcinogens; D005449:Fluorenes; D011721:Pyrenes; C012177:2-aminofluorene; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; C004482:1-aminopyrene; C032668:1-nitropyrene