title: The formation of AFB(1)-macromolecular adducts in rats and humans at dietary levels of exposure.
abstract: The levels of aflatoxin B(1)-DNA and aflatoxin B(1)-albumin adducts were investigated by accelerator mass spectrometry (AMS) in humans and rats following exposure to a known, dietary relevant amount of carbon-14 labeled aflatoxin B(1) ([(14)C]AFB(1)). The aims of the study were to: (a) investigate the dose-dependent formation of DNA and protein adducts at very low doses of AFB(1) (0.16 ng/kg-12.3 microg/kg) in the rat; (b) measure the levels of AFB(1)-albumin and AFB(1)-DNA adducts at known, relevant exposures in humans (c) study rat to human extrapolations of AFB(1)-albumin and DNA adduct levels. The results in the rat showed that both AFB(1)-albumin adduct and AFB(1)-DNA adduct formation were linear over this wide dose range. The order of adduct formation within the tissues studied was liver>kidney>colon>lung=spleen. Consenting volunteers received 1 microg ( approximately 15 ng/kg) of [(14)C]AFB(1) in a capsule approximately approximately 3.5-7 h prior to undergoing colon surgery. The mean level of human AFB(1)-albumin adducts was 38.8+/-19.55 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg body weight (b.w.), which was not statistically different to the equivalent dose in the rat (15 ng/kg) 42.29+/-7.13 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg b.w. There was evidence to suggest the formation of AFB(1)-DNA adducts in the human colon at very low doses. Comparison of the linear regressions of hepatic AFB(1)-DNA adduct and AFB(1)-albumin adduct levels in rat found them to be statistically similar suggesting that the level of AFB(1)-albumin adducts are useful biomarkers for AFB(1) dosimetry and may reflect the DNA adduct levels in the target tissue. [(14)C]AFB(1)-DNA and [(14)C]AFB(1)-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [(14)C] measured by AMS was derived from the expected [(14)C]AFB(1) adducts.
authors.affiliation: Jack Birch Unit for Environmental Carcinogenesis, Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: B C
authors.initials: BC
authors.lastname: Cupid
authors.forename: T J
authors.initials: TJ
authors.lastname: Lightfoot
authors.forename: D
authors.initials: D
authors.lastname: Russell
authors.forename: S J
authors.initials: SJ
authors.lastname: Gant
authors.forename: P C
authors.initials: PC
authors.lastname: Turner
authors.forename: K H
authors.initials: KH
authors.lastname: Dingley
authors.forename: K D
authors.initials: KD
authors.lastname: Curtis
authors.forename: S H
authors.initials: SH
authors.lastname: Leveson
authors.forename: K W
authors.initials: KW
authors.lastname: Turteltaub
authors.forename: R C
authors.initials: RC
authors.lastname: Garner
mesh_terms: D016604:Aflatoxin B1 / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D000348:Aflatoxins / Q000032:analysis / Q000378:metabolism*; D000418:Albumins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D012588:Scintillation Counting
chemical_list: D000348:Aflatoxins; D000418:Albumins; D002273:Carcinogens; D018736:DNA Adducts; C098408:aflatoxin-albumin adduct; D016604:Aflatoxin B1