title: Urinary excretion of 3-methyladenine after consumption of fish containing high levels of dimethylamine.
abstract: The urinary excretion of the DNA alkylation product, 3-methyladenine (3-MeAde), was measured in human volunteers who were on controlled diets and consumed fresh fish, or frozen-stored fish that contained 50-fold higher levels of dimethylamine (DMA), with or without ingested nitrate. DMA potentially could react with nitrosating agents in the diet or within the body, and produce the potent carcinogen N-nitrosodimethylamine (NDMA), which can then react with DNA to form several adducts including 3-MeAde. Our findings show that there was no increase in urinary levels of 3-MeAde after consumption of fish preserved by frozen storage relative to levels after consumption of fresh fish. Furthermore, consumption of 225 mg sodium nitrate (equal to the nitrate content in a large glass of beet juice) at 1 h prior to consumption of the frozen-stored fish did not increase urinary 3-MeAde levels as would be expected if nitrate enhanced endogenous nitrosation of DMA. In contrast, urinary excretion of 3-MeAde from a volunteer who was a moderate cigarette smoker (11 cigarettes per day) was approximately 3- to 8-fold higher than dietary 3-MeAde intake. These findings indicate that consumption of high levels of DMA in fish does not result in detectable levels of NDMA formation and genetic damage as measured by the urinary biomarker 3-MeAde.
authors.affiliation: Nestle Research Center, Nestec Ltd, Lausanne, Switzerland.
authors.forename: L B
authors.initials: LB
authors.lastname: Fay
authors.forename: C D
authors.initials: CD
authors.lastname: Leaf
authors.forename: E
authors.initials: E
authors.lastname: Gremaud
authors.forename: J M
authors.initials: JM
authors.lastname: Aeschlimann
authors.forename: C
authors.initials: C
authors.lastname: Steen
authors.forename: D E
authors.initials: DE
authors.lastname: Shuker
authors.forename: R J
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D004032:Diet; D004123:Dimethylamines / Q000378:metabolism*; D005399:Fishes; D005519:Food Preservation; D005615:Freezing; D006801:Humans; D008744:Methylamines / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism
chemical_list: D004123:Dimethylamines; D008744:Methylamines; D009566:Nitrates; D009602:Nitrosamines; D009603:Nitroso Compounds; C008651:4-nitrosodimethylaniline; C025946:3-methyladenine; C034516:dimethylamine; D000225:Adenine; C023336:trimethylamine