O(6)-methylguanine DNA adducts associated with occupational nitrosamine exposure.
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(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 occupational personal breathing zone (PBZ) nitrosamine exposures ranged from 0.4 to 9.3 microg/m(3) in the VS area, from 0.1-2 microg/m(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(7)mdG adducts, ranging 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 (median 3.60 compared with 1.44), the difference was not statistically significant after controlling for confounding factors. The O(6)mdG adduct concentrations 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 participants (40/78 successfully analyzed) did not have detectable amounts of these adducts (limit of detection 0.03 O(6)mdG adducts/10(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(6)mdG adducts (Kendall's taub = -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(7)mdG adduct concentrations or AGT activity, the significant positive association between working in and near the VS department and the presence of O(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.
Reh
B D
BD
NIOSH/DSHEFS/HETAB, 4676 Columbia Parkway, Mailstop R-11, Cincinnati, OH 45226, USA. byd3@cdc.gov
DeBord
D G
DG
Butler
M A
MA
Reid
T M
TM
Mueller
C
C
Fajen
J M
JM
D018736:DNA Adducts / Q000032:analysis*; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D009602:Nitrosamines / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D016273:Occupational Exposure; D012408:Rubber
D018736:DNA Adducts; D009602:Nitrosamines; D006147:Guanine; C008450:7-methylguanine; D012408:Rubber; C008449:O-(6)-methylguanine; D019853:O(6)-Methylguanine-DNA Methyltransferase