O super(6)-methylguanine DNA adducts associated with occupational nitrosamine exposure

• Published in: Carcinogenesis (New York) Vol. 21; no. 1; pp. 29 - 33
• Main Authors: Reh, B D, DeBord, D G, Butler, MA, Reid, T M, Mueller, C, Fajen, J M
• Format: Journal Article
• Language: English
• Published: 01.01.2000
• ISSN: 0143-3334

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, N super(7)-methylguanine (N super(7)mdG) and O super(6)-methylguanine (O super(6)mdG), and with the activity of the enzyme that repairs O super(6)mdG adducts, O super(6)-alkylguanine-DNA alkyltransferase (AGT). The occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 mu g/m super(3) in the VS area, from 0.1-2 mu g/m super(3) 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 N super(7)mdG adducts, ranging from 0.1 to 133.2 adducts/10 super(7) deoxyguanosine nucleosides. Although N super(7)mdG 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 O super(6)mdG adduct concentrations were much lower than those of N super(7)mdG, ranging from non-detectable to 12.7 O super(6)mdG adducts/10 super(7) deoxyguanosine nucleosides and many of the participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O super(6)mdG adducts/10 super(7) 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 O super(6)mdG adducts (Kendall's -b = -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 N super(7)mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O super(6)mdG 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.