O-6-methylguanine DNA adducts associated with occupational nitrosamine exposure

Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing o peration were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N-7-methylguanine (N(7)mdG) and O-6 -methylguanine (O(6)mdG), and with the activity of the enzyme that repairs O(6)mdG adducts, O-6-alkylguanine-DNA alkyltransferase (AGT), The occupatio nal personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 mu g/m(3) in the VS area, from 0.1-2 mu g/m(3) in an area remote from t he VS and were not detected at a nearby rubber plant. Workers from all thre e of these locations had detectable concentrations of N(7)mdG adducts, rang ing from 0.1 to 133.2 adducts/10(7) deoxyguanosine nucleosides. Although N( 7)mdG concentrations were elevated for those who worked in the VS area (med ian 3.60 compared with 1.44), the difference was not statistically signific ant after controlling for confounding factors. The O(6)mdG adduct concentra tions were much lower than those of N(7)mdG, ranging from non-detectable to 12.7 O(6)mdG adducts/10(7) deoxyguanosine nucleosides and many of the part icipants (40/78 successfully analyzed) did not have detectable amounts of t hese adducts (limit of detection 0.03 O(6)mdG adducts/10(7) deoxyguanosine nucleosides). Analysis of the ordinal exposure categories thigh, medium/hig h, medium/low, low and no exposure) yielded a statistically significant ass ociation with having detectable O(6)mdG adducts (Kendall's tau b = -0.253, asymptotic SE = 0.096). There was no significant association between AGT ac tivity and nitrosamine exposure or exposure category (P > 0.30). Although n o association was found between PBZ exposure and either the N(7)mdG adduct concentrations or AGT activity, the significant positive association betwee n working in and near the VS department and the presence of O(6)mdG adducts , which have mutagenic potential, provides evidence to link nitrosamine exp osure one step closer to human cancer by demonstrating an association betwe en external nitrosamine exposures and cancer-related biological effects.