Abstract
The structure and previous studies on the biotransformation of toluene lead to the suspicion that metabolites may be formed which preferentially react with strongly nucleophilic partners such as sulfhydryl groups of cysteines in proteins. Human 8-oxoguanine DNA glycosylase 1 removes the major oxidative DNA damage and possesses eight cysteines. Its potential inactivation may lead to accumulation of DNA damage by reactive oxygen species formed by exogenous agents or by ubiquitous endogenous processes. The goal of the present investigation was to study the in vivo effect in humans of an acute toluene exposure on hOGG1 activity. Twenty healthy, non-smoking males were exposed to 50 ppm toluene and to filtered air in an exposure chamber for 270 min, using a cross-over design. Before and 30 min after the end of exposure, blood samples were taken and toluene concentrations and the hOGG1 activity were measured. hOGG1 activity was determined in peripheral mononuclear blood cells. Thirty minutes after exposure to toluene, we found a median blood concentration of 0.25 mg toluene/l. Compared with the activity before exposure, upon exposure to toluene a statistically insignificant median increase of hOGG1 activity by +0.4% and upon exposure to air by +2.3% was determined. Thus, no reduction of the hOGG1 repair activity after acute exposure to 50 ppm toluene was observed.
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References
Andersen I, Lundquist GR, Molhave L et al (1983) Human response to controlled levels of toluene in six-hour exposures. Scand J Work Environ Health 9:405–418
Boiteux S, Radicella JP (1999) Base excision repair of 8-hydroxyguanine protects DNA from endogenous oxidative stress. Biochimie 81:59–67. doi:10.1016/S0300-9084(99)80039-X
Boyum A (1964) Separation of white blood cells. Nature 204:793–794. doi:10.1038/204793a0
Bravard A, Vacher M, Gouget B et al (2006) Redox regulation of human OGG1 activity in response to cellular oxidative stress. Mol Cell Biol 26:7430–7436. doi:10.1128/MCB.00624-06
Cheng KC, Cahill DS, Kasai H et al (1992) 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions. J Biol Chem 267:166–172
Chevillard S, Radicella JP, Levalois C et al (1998) Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours. Oncogene 16:3083–3086. doi:10.1038/sj.onc.1202096
Collins AR, Cadet J, Möller L et al (2004) Are we sure we know how to measure 8-oxo-7, 8-dihydroguanine in DNA from human cells? Arch Biochem Biophys 423:57–65. doi:10.1016/j.abb.2003.12.022
DFG (2006) Benzene and alkylbenzenes (BTX aromatics). In: Angerer J (ed) The MAK-collection: essential biomonitoring methods. Wiley-VCH, Weinheim, pp 169–192
Gerin M, Siemiatycki J, Desy M et al (1998) Associations between several sites of cancer and occupational exposure to benzene, toluene, xylene, and styrene: results of a case-control study in Montreal. Am J Ind Med 34:144–156. doi:10.1002/(SICI)1097-0274(199808)34:2<144::AID-AJIM7>3.0.CO;2-X
Hammer KD, Mayer N, Pfeiffer EH (1998) Sister chromatid exchanges in rotogravure printing plant workers. Int Arch Occup Environ Health 71:138–142. doi:10.1007/s004200050261
Hartwig A, Asmuss M, Ehleben I et al (2002) Interference by toxic metal ions with DNA repair processes and cell cycle control: molecular mechanisms. Environ Health Perspect 110(Suppl 5):797–799
Hazra TK, Hill JW, Izumi T et al (2001) Multiple DNA glycosylases for repair of 8-oxoguanine and their potential in vivo functions. Prog Nucleic Acid Res Mol Biol 68:193–205. doi:10.1016/S0079-6603(01)68100-5
IARC (1999) Toluene. In: Monographs on the evaluation of carcinogenic risks to humans, vol 71: re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. Frankreich, Lyon, pp 829–864
Iregren A, Gamberale F, Kjellberg A (1996) SPES: a psychological test system to diagnose environmental hazards. Neurotoxicol Teratol 18:485–491. doi:10.1016/0892-0362(96)00033-5
Janssen K, Schlink K, Götte W et al (2001) DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326. Mutat Res 486:207–216
Kim HN, Morimoto Y, Tsuda T et al (2001) Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos. Carcinogenesis 22:265–269. doi:10.1093/carcin/22.2.265
Landi MT, Sinha R, Lang NP et al (1999) Human cytochrome P4501A2. IARC Sci Publ (148):173–195
Lehmacher W (1987) Verlaufskurven und crossover. In: Überla K, Reichertz PL, Victor N (eds) Medizinische informatik und statistik. Springer, Berlin, pp 79–105
Lutz WK (1984) Structural characteristics of compounds that can be activated to chemically reactive metabolites: use for a prediction of carcinogenic potential. Arch Toxicol Suppl 7:194–207
Mazzullo M, Bartoli S, Bonora B et al (1989) Benzene adducts with rat nucleic acids and proteins: dose–response relationship after treatment in vivo. Environ Health Perspect 82:259–266. doi:10.2307/3430784
Murata M, Tsujikawa M, Kawanishi S (1999) Oxidative DNA damage by minor metabolites of toluene may lead to carcinogenesis and reproductive dysfunction. Biochem Biophys Res Commun 261:478–483. doi:10.1006/bbrc.1999.1041
Nakajima T (1997) Cytochrome P450 isoforms and the metabolism of volatile hydrocarbons of low relative molecular mass. J Occup Health 39:83–91. doi:10.1539/joh.39.83
National Institute of Occupational Health (NIOSH) National Occupational Exposure Survey (1983) http://www.cdc.gov/noes/
Pathiratne A, Puyear RL, Brammer JD (1986) Activation of 14C-toluene to covalently binding metabolites by rat liver microsomes. Drug Metab Dispos 14:386–391
Seeber A, Blaszkewicz M, Kiesswetter et al (1994) Biomonitoring, Leistung und Befinden bei inhalativer Ethanolexposition. In: Kessel R (ed) Verhandlungen der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin, vol. 34, Jahrestagung. Gentner, Stuttgart, pp 205–209
Seifert T (2002) Analyse der DNS-Reparaturaktivität der humanen 8-Oxoguanin-Glykosylase 1 (hOGG1) in peripheren mononukleären Zellen lösungsmittelexponierter Arbeiter und Probanden. Ph.D. Thesis, University of Mainz
Svensson BG, Nise G, Englander V et al (1990) Deaths and tumours among rotogravure printers exposed to toluene. Br J Ind Med 47:372–379
van Houten V, Denkers F, van Dijk M, van den Brekel M, Brakenhoff R (1998) Labeling efficiency of oligonucleotides by T4 polynucleotide kinase depends on 5′-nucleotide. Anal Biochem 265:386–389. doi:10.1006/abio.1998.2900
Warshawsky D, Barkley W, Bingham E (1993) Factors affecting carcinogenic potential of mixtures. Fundam Appl Toxicol 20:376–382. doi:10.1006/faat.1993.1048
Acknowledgments
We thank ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: Food Quality and Safety (Contract no. 513943) for financial support.
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Finkenwirth, P., Spelmeyer, U., Hommel, G. et al. Effects of an acute exposure to toluene on the DNA repair activity of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) in healthy subjects. Arch Toxicol 83, 777–784 (2009). https://doi.org/10.1007/s00204-009-0415-1
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DOI: https://doi.org/10.1007/s00204-009-0415-1