Journal Article

<i>O</i><sup>6</sup>-methylguanine DNA adducts associated with occupational nitrosamine exposure

Beth Donovan Reh, D.Gayle DeBord, Mary Ann Butler, Thomas M. Reid, Charles Mueller and John M. Fajen

in Carcinogenesis

Volume 21, issue 1, pages 29-33
Published in print January 2000 | ISSN: 0143-3334
Published online January 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.1.29
O6-methylguanine DNA adducts associated with occupational nitrosamine exposure

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Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N7-methylguanine (N7mdG) and O6-methylguanine (O6mdG), and with the activity of the enzyme that repairs O6mdG adducts, O6-alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 μg/m3 in the VS area, from 0.1–2 μg/m3 in an area remote from the VS and were not detected at a nearby rubber plant. Workers from all three of these locations had detectable concentrations of N7mdG adducts, ranging from 0.1 to 133.2 adducts/107 deoxyguanosine nucleosides. Although N7mdG concentrations were elevated for those who worked in the VS area (median 3.60 compared with 1.44), the difference was not statistically significant after controlling for confounding factors. The O6mdG adduct concentrations were much lower than those of N7mdG, ranging from non-detectable to 12.7 O6mdG adducts/107 deoxyguanosine nucleosides and many of the participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O6mdG adducts/107 deoxyguanosine nucleosides). Analysis of the ordinal exposure categories (high, medium/high, medium/low, low and no exposure) yielded a statistically significant association with having detectable O6mdG adducts (Kendall's τb = −0.253, asymptotic SE = 0.096). There was no significant association between AGT activity and nitrosamine exposure or exposure category (P > 0.30). Although no association was found between PBZ exposure and either the N7mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O6mdG adducts, which have mutagenic potential, provides evidence to link nitrosamine exposure one step closer to human cancer by demonstrating an association between external nitrosamine exposures and cancer-related biological effects.

Keywords: AGT, O6-alkylguanine-DNA alkyltransferase; BMI, body mass index; dG, deoxyguanosine 3′-monophosphate; NDBA, nitrosodibutylamine; NDEA, nitrosodiethylamine; NDMA, nitrosodimethylamine; NDPA, nitrosodipropylamine; NIOSH, National Institute for Occupational Safety and Health; N7mdG, N7-methylguanine; NMOR, nitrosomorpholine; NPIP, nitrosopiperidine; NPYR, nitrosopyrrolidine; O6mdG, O6-methylguanine; PBZ, personal breathing zone; RFLP, restriction fragment length polymorphism; SIM, selected ion monitoring; VS, vehicle seal.

Journal Article.  4730 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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