title: Analysis of N-alkylated amino acids in human hemoglobin: evidence for elevated N-methylvaline levels in smokers.
abstract: To investigate the contribution of cigarette smoking to the levels of N-methylvaline and N-hydroxyethylvaline in hemoglobin we analyzed samples from 32 smokers and 37 nonsmokers. The average background levels of the nonsmoking individuals were determined to be 1175 +/- 176 pmol N-methylvaline/g globin, ranging from 722 to 1516 pmol/g globin, and 46 +/- 12 pmol N-hydroxyethylvaline/g globin, ranging from 19 to 64 pmol/g globin. A significant correlation (P < 0.001) was found between both amino acids and the amount of cigarettes smoked per day, with an increase of 42 pmol N-methylvaline/g globin/cigarette per day and 11 pmol N-hydroxyethylvaline/g globin/cigarette per day. No influence of age, sex, and occupational exposure was observed. Furthermore, the levels of N-hydroxyethylvaline and N-methylvaline correlated for smokers but not for nonsmokers, indicating cigarette smoking as a common source for both adducts. To our knowledge, this is the first time N-methylvaline levels are reported to differ significantly between smokers and nonsmokers in the general population. Especially the analysis of N-methylvaline following low-level exposures to methylating agents should therefore take into consideration the influence of individual smoking habits. Additionally, the results of our study confirm the reliability of N-hydroxyethylvaline as an indicator of individual cigarette consumption. We successfully applied a new calibration technique to the analysis of N-hydroxyethylvaline, introducing a commercially available and well-defined dipeptide standard. The observed levels of N-hydroxyethylvaline in the samples are in line with those reported in the literature and verify the applicability of our calibration method.
authors.affiliation: Institute and Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nümberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: J
authors.initials: J
authors.lastname: Lewalter
authors.forename: J
authors.initials: J
authors.lastname: Angerer
mesh_terms: D000328:Adult; D002138:Calibration; D005260:Female; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012907:Smoking / Q000097:blood*; D014633:Valine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D006454:Hemoglobins; D014633:Valine