Interindividual differences in the activation of two hepatic carcinogens to mutagens by human liver.
The possibility that the presence of malignant disease can influence the metabolic activation of two carcinogens, 2-acetylaminofluorene and aflatoxin B1, has been investigated in a group of patients with secondary carcinoma of the liver. Mutagenic activation by subcellular fractions from biopsy samples from the patients was determined in the Ames/Salmonella test and the results compared with those obtained from a group of control patients. No significant differences were observed between the groups of patients in their ability to activate the two compounds to mutagenic metabolites. A tenfold range in ability to activate aflatoxin B1 was observed whereas only a threefold range was obtained with 2-acetylaminofluorene. Human liver activates aflatoxin B1 approximately 100 times more efficiently than 2-acetylaminofluorene, a proven carcinogen in many species. This raises the question of the true risk to man from hepatocarcinogenicity from aflatoxin B1.
Harries
G C
GC
Boobis
A R
AR
Collier
N
N
Davies
D S
DS
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity; D000469:Alkaline Phosphatase / Q000097:blood; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism* / Q000556:secondary; D009152:Mutagenicity Tests; D013347:Subcellular Fractions / Q000378:metabolism
D000348:Aflatoxins; D002273:Carcinogens; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin