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Analysis of N-alkylated amino acids in human hemoglobin: evidence for elevated N-methylvaline levels in smokers

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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.

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References

  • Bader M, Angerer J (1994) Strategies for the biological monitoring of benzene exposure by the GC/MS determination of protein adducts. 2nd European Workshop on Mass Spectrometry in Occupational Health, Les Diablerets, Switzerland, June 16–18

    Google Scholar 

  • Bailey E, Brooks AGF, Dollery CT, Farmer PB, Passingham BJ, Sleightholm MA, Yates DW (1988) Hydroxyethylvaline adduct formation in haemoglobin as a biological monitor of cigarette smoke intake. Arch Toxicol62:247–253

    Google Scholar 

  • Christakopoulos A, Bergmark E, Zorcec V, Norppa H, Mäki-Paakkanen J, Osterman-Golkar S (1993) Monitoring occupational exposure to styrene from hemoglobin adducts and metabolites in blood. Scand J Work Environ Health 19:255–263

    Google Scholar 

  • Day BW, Naylor S, Gan LS, Sahali Y, Nguyen TT (1991) Gas chromatographic- mass spectrometric analysis of diols and tetrols from reactions of polycyclic aromatic hydrocarbon epoxides with hemoglobin. J Chromatogr Biomed Appl 562:563–571

    Google Scholar 

  • DIN (1991) Chemical analysis. Detection limit, identification limit and determination limit (DIN 32645 E). Deutsches Institut für Normung e.V. Beuth, Berlin

    Google Scholar 

  • Ehrenberg L, Osterman-Golkar S (1980) Alkylation of macromolecules for detecting mutagenic agents. Teratogen Carcinogen Mutagen 1:105–127

    Google Scholar 

  • Garner RC (1985) Assessment of carcinogen exposure in man. Carcinogenesis 6:1071–1078

    Google Scholar 

  • Kautiainen A, Törngvist M (1991) Monitoring exposure to simple epoxides and alkenes through gas chromatographic determination of hemoglobin adducts. Int Arch Occup Environ Health 63:27–31

    Google Scholar 

  • Letzel S, Holz O, Drexler H, Weber A, Angerer J, Weltle J, Rüdiger HW, Sladeczek F, Lehnert G (1993) Untersuchung zur Objektivierung und Quantifizierung einer beruflichen 1,3-Butadien-Belastung. In: Triebig G, Stelzer O (eds) Verhandlungen der Deutschen Gesellschaft für Arbeits- und Umweltmedizin e.V. Gentner, Stuttgart, pp 629–633

    Google Scholar 

  • Lewalter J, Ellrich D, Müller G, Norpoth K (1993) Der N-Alkyl-Valin-Gehalt im Globin des Erythrocyten als Bio-Marker der Belastungen durch Alkylantien. In: Triebig G, Stelzer O (eds) Verhandlungen der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizine e.V. Gentner, Stuttgart, pp 437–443

    Google Scholar 

  • Mowrer J, Törngvist M, Jensen S, Ehrenberg L (1986) Modified Edman degradation applied to hemoglobin for monitoring occupational exposure to alkylating agents. Toxicol Environ Chem 11:215–231

    Google Scholar 

  • Neumann HG (1988) Neue Wege der Expositionskontrolle bei krebserzeugenden Substanzen. ErgoMed 2:26–31

    Google Scholar 

  • Osterman-Golkar S, Kautiainen A, Bergmark E, Håkansson, Mäki-Paakkanen J (1991) Hemoglobin adducts and urinary mercapturic acids in rats as biological indicators of butadiene exposure. Chem Biol Interact 80:291–302

    Google Scholar 

  • Sabbioni G (1992) Hemoglobin binding of monocyclic aromatic amines: molecular dosimetry and quantitative structure activity relationships for the N-oxidation. Chem Biol Interact 81:91–117

    Google Scholar 

  • Sarto F, Torngvist M, Tomanin R, Bartolucci GB, Osterman-Golkar S, Ehrenberg L (1991) Studies of biological and chemical monitoring of low-level exposure to ethylene oxide. Scand J Work Environ Health 17:60–64

    Google Scholar 

  • Skipper PL, Tannenbaum SR (1990) Protein adducts in the molecular dosimetry of chemical carcinogens. Carcinogenesis 11:507–518

    Google Scholar 

  • Skipper PL, Peng X, Soohoo CK, Tannenbaum SR (1994) Protein adducts as biomarkers of human carcinogen exposure. Drug Metab Rev 26:111–124

    Google Scholar 

  • Törnqvist M (1991) The N-alkyl Edman method for haemoglobin adduct measurement: updating and applications to humans. In: Garner RC, Farmer PB, Steel GT, Wright AS (eds) Human carcinogen exposure: biomonitoring and risk assessment. Oxford University Press, Oxford, pp 411–419

    Google Scholar 

  • Törnqvist M, Mowrer J, Jensen S, Ehrenberg L (1986a) Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method. Anal Biochem 154:255–266

    Google Scholar 

  • Törnqvist M, Osterman-Golkar S, Kautiainen A, Jensen S, Farmer PB, Ehrenberg L (1986b) Tissue doses of ethylene oxide in cigarette smokers determined from adduct levels in hemoglobin. Carcinogenesis 7:1519–1521

    Google Scholar 

  • Törnqvist M, Osterman-Golkar S, Kautiainen A, Näslund M, Calleman CJ, Ehrenberg L (1988a) Methylations in human hemoglobin. Mutat Res 204:521–529

    Google Scholar 

  • Törnqvist M, Kautiainen A, Gatz RN, Ehrenberg L (1988b) Hemoglobin adducts in animals exposed to gasoline and diesel exhausts. 1. Alkenes. J Appl Toxicol 8:159–170

    Google Scholar 

  • Törnqvist M, Svartengren M, Ericsson CH (1992a) Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors. Chem Biol Interact 82:91–98

    Google Scholar 

  • Törnqvist M, Magnusson AL, Farmer PB, Tang YS, Jeffrey AM, Wazneh L, Beulink GDT, van der Waal H, van Sittert NJ (1992b) Ring test for low levels of N-(2-hydroxyethyl)valine in human hemoglobin. Anal Biochem 203:357–360

    Google Scholar 

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Bader, M., Lewalter, J. & Angerer, J. Analysis of N-alkylated amino acids in human hemoglobin: evidence for elevated N-methylvaline levels in smokers. Int. Arch Occup Environ Heath 67, 237–242 (1995). https://doi.org/10.1007/BF00409405

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