Protection by dietary compounds against mutation in a transgenic rodent.
One of the most relevant biomarkers of genotoxicity and, potentially, carcinogenesis is the occurrence of mutations. Data indicate that carcinogens are highly specific with regard to their target tissue in inducing both tumors and mutations. This specificity may reflect the dependence on tissue-specific metabolic activation, the organ-specific environment or both. Ideally, therefore, mutation should be determined in a real animal rather than in a cell culture system. The lacI transgenic rodent model provides such a system. We have used this model to investigate tissue, species and sex specificity of mutation induced by selected dietary carcinogens and to examine how some compounds may alter the induction of mutation. We have studied mutation using several chemicals, including the dietary heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the environmentally important aromatic hydrocarbon benzo[a]pyrene and the food contaminant aflatoxin B1. We have shown that the mutagenic potency of these chemicals can be modulated by other dietary compounds, including green tea and conjugated linoleic acid, and the dioxin 2,3,7,8-tetrachlorodibenzo[b,e][1,4]dioxin (TCDD). These results demonstrate that the lacI transgenic rodent is a useful model for the study of chemoprevention in vivo.
de Boer
J G
JG
Centre for Environmental Health, University of Victoria, Victoria, British Columbia, Canada. jdboer@uvic.ca
D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D030801:Animals, Genetically Modified; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D004195:Disease Models, Animal; D029968:Escherichia coli Proteins; D006801:Humans; D007093:Imidazoles / Q000633:toxicity; D056968:Lac Repressors; D051379:Mice; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009369:Neoplasms / Q000178:diet therapy / Q000517:prevention & control*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012727:Sex Characteristics; D013045:Species Specificity
D001426:Bacterial Proteins; D002273:Carcinogens; D029968:Escherichia coli Proteins; D007093:Imidazoles; D056968:Lac Repressors; D009153:Mutagens; D012097:Repressor Proteins; D001564:Benzo(a)pyrene; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D016604:Aflatoxin B1