title: CYP1A2 and NAT2 phenotyping and 3-aminobiphenyl and 4-aminobiphenyl hemoglobin adduct levels in smokers and non-smokers.
abstract: Some aromatic amines are considered to be putative bladder carcinogens. Hemoglobin (Hb) adducts of 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP) have been used as biomarkers of exposure to aromatic amines from cigarette smoke. One of the goals of this study was to determine intra- and inter-individual variability in 3-ABP and 4-ABP Hb adducts and to explore the predictability of ABP Hb adduct levels based on caffeine phenotyping. The study was conducted in adult smokers (S, n = 65) and non-smokers (NS, n = 65). The subjects were phenotyped for CYP1A2 and NAT2 using urinary caffeine metabolites. Blood samples were collected twice within 6 weeks and adducts measured by GC/MS. The levels of 4-ABP Hb adducts were significantly (p < 0.0001) greater in S (34.5 +/- 21.06 pg/g Hb) compared to NS (6.3 +/- 3.02 pg/g Hb). The levels of 3-ABP Hb adducts were below the limit of quantification (BLOQ) in most (82%) of the NS and about 10-fold lower in S (3.6 +/- 3.29 pg/g Hb) compared to 4-ABP Hb adducts. No differences were observed in the adduct levels between weeks 1 and 6 in the smokers, suggesting that a single sample would be adequate to monitor cigarette smoke exposure. The regression model developed with CYP1A2, NAT2 phenotype and number of cigarettes smoked (NCIG) accounted for 47% of the variability in 3-ABP adducts, whereas 32% variability in 4-ABP adducts was accounted by CYP1A2 and NCIG. The ratio of 4-ABP Hb adducts in adult S:NS was approximately 5:1, whereas 3-ABP Hb adducts levels were BLOQ in some S, exhibited large interindividual variability ( approximately 91% compared to 57% for 4-ABP Hb) and poor dose response relationship. Therefore, 4-ABP Hb adduct levels may be a more useful biomarker of aminobiphenyl exposure from cigarette smoke.
authors.affiliation: Philip Morris U.S.A., Richmond, VA 23261, USA. mohamadi.sarkar@pmusa.com
authors.forename: Mohamadi
authors.initials: M
authors.lastname: Sarkar
authors.forename: Regina
authors.initials: R
authors.lastname: Stabbert
authors.forename: Robin D
authors.initials: RD
authors.lastname: Kinser
authors.forename: Jan
authors.initials: J
authors.lastname: Oey
authors.forename: Klaus
authors.initials: K
authors.lastname: Rustemeier
authors.forename: Klaus
authors.initials: K
authors.lastname: von Holt
authors.forename: Georg
authors.initials: G
authors.lastname: Schepers
authors.forename: Roger A
authors.initials: RA
authors.lastname: Walk
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Roethig
mesh_terms: D000328:Adult; D000368:Aged; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D015415:Biomarkers; D002273:Carcinogens / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011485:Protein Binding; D012907:Smoking / Q000378:metabolism*
chemical_list: D000611:Aminobiphenyl Compounds; D015415:Biomarkers; D002273:Carcinogens; D006454:Hemoglobins; C006757:4-biphenylamine; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C049671:3-aminobiphenyl