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O6-methylguanine DNA adducts associated with occupational nitrosamine exposure.
Reh-BD; DeBord-DG; Butler-MA; Reid-TM; Mueller-C; Fajen-JM
Carcinogenesis 2000 Jan; 21(1):29-33
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 06-methylguanine (O6mdG), and with the activity of the enzyme that repairs 06mdG adducts, 06- alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 ug/m3 in the VS area, from 0.1-2 ug/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/l07 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 06mdG adduct concentrations were much lower than those of N7mdG, ranging from non-detectable to 12.7 06mdG adducts/lO' deoxyguanosine nucleosides and many of the participants (40nS successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 06mdG adducts/l07 deoxyguanosine nucleosides). Analysis of the ordinal exposure categories (high, medium/high, medium/low and no exposure) yielded a statistically significant association with having detectable 06mdG adducts (Kendall's tb = -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 06mdG 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.
Occupational-exposure; Blood-analysis; Blood-tests; Rubber-workers; Rubber-manufacturing-industry; Breathing-zone; Cancer; Biological-effects
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Page last reviewed: April 12, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division