title: Gene-diet interactions in exposure to heterocyclic aromatic amines and bulky DNA adduct levels in blood leukocytes.
abstract: Heterocyclic aromatic amines (HAAs), carcinogens produced in meat when cooked at high temperatures, are an emerging biologic explanation for the meat-colorectal cancer relationship. HAAs form DNA adducts; left unrepaired, adducts can induce mutations, which may initiate/promote carcinogenesis. The purpose of this research was to investigate the relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct levels. Least squares regression was used to examine the relationship between dietary HAA exposure and bulky DNA adduct levels in blood measured using (32)P-postlabeling among 99 healthy volunteers. Gene-diet interactions between dietary HAAs and genetic factors relevant to the biotransformation of HAAs and DNA repair were also examined. No main effects of dietary HAAs on bulky DNA adduct levels was found. However, those with the putative NAT1 rapid acetylator phenotype had lower adduct levels than those with the slow acetylator phenotype (P = 0.02). Furthermore, having five or more 'at-risk' genotypes was associated with higher bulky DNA adduct levels (P = 0.03). Gene-diet interactions were observed between NAT1 polymorphisms and dietary HAAs (P < 0.05); among the slow acetylator phenotype, higher intakes of HAAs were associated with an increase in DNA adduct levels compared to lower intakes. This study provides evidence of a biologic relationship between dietary HAAs, genetic susceptibility and bulky DNA adduct formation. However, the lack of a strong main effect of HAAs suggests that dietary HAAs are not a large contributor to bulky DNA adducts in this population; future studies should consider relevant gene-diet interactions to clarify the role of HAAs in carcinogenesis.
authors.affiliation: University of Montreal Hospital Research Centre (CRCHUM), Tour Saint-Antoine, Montréal, Québec, H2X 0A9, Canada.
authors.forename: Vikki
authors.initials: V
authors.lastname: Ho
authors.affiliation: Department of Public Health Sciences, Queen's University, Kingston, Ontario, K7L3N6, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Peacock
authors.affiliation: Department of Biomedical and Molecular Sciences, Pharmacology and Toxicology Graduate Program, Kingston, Ontario, K7L3N6, Canada.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Massey
authors.affiliation: Department of Toxicology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.affiliation: Department of Toxicology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: Department of Pathology, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Public Health Sciences, Queen's University, Kingston, Ontario, K7L3N6, Canada.
authors.forename: Will D
authors.initials: WD
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D000588:Amines / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D059647:Gene-Environment Interaction; D006571:Heterocyclic Compounds / Q000633:toxicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D008460:Meat; D008875:Middle Aged; D017422:Sequence Analysis, DNA
chemical_list: D000588:Amines; D002273:Carcinogens; D018736:DNA Adducts; D006571:Heterocyclic Compounds
keywords: 32P-postlabelling; DNA adducts; MeIQx; PhIP; carcinogens; n-acetyltransferase 1