Prostate mutations in rats induced by the suspected human carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
Male lacl transgenic rats were fed a diet containing 200 ppm of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine present in cooked meats. PhIP was found to be a powerful prostate mutagen. After 61 days of treatment, the lacl mutant frequency was 71 x 10(-5), >20-fold higher than the spontaneous mutant frequency of 3.2 x 10(-5). The predominant PhIP-induced mutations were G:C->T:A transversions and deletions of G:C bp. The results directly link PhIP-induced mutations with the earlier observation of PhIP-induced prostate cancer in rats and suggest that exposure to dietary PhIP could be a risk factor in the incidence of human prostate cancer.
Stuart
G R
GR
Centre for Environmental Health and Department of Biology, University of Victoria, British Columbia, Canada.
Holcroft
J
J
de Boer
J G
JG
Glickman
B W
BW
D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity*; D029968:Escherichia coli Proteins; D016368:Frameshift Mutation; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D056968:Lac Repressors; D008297:Male; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion
D001426:Bacterial Proteins; D002273:Carcinogens; D029968:Escherichia coli Proteins; D007093:Imidazoles; D056968:Lac Repressors; D009153:Mutagens; D012097:Repressor Proteins; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine