Elevated somatic mutations at the glycophorin a (GPA) locus are associated with PAH exposure in Finnish iron foundry workers
- Univ. of Pittsburgh Cancer Institute, PA (United States)
- Columbia Univ., New York, NY (United States); and others
The potential genotoxic effect of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) was assessed using the GPA-based in vivo somatic cell mutation assay in a group of 39 iron foundry workers. Individual exposures to benzo[a]pyrene (B[a]P) over a four-year period were estimated using job titles together with personal and area monitoring data. Blood samples, collected over the same period, were analyzed for the frequency of variant erythroyctes expressing GPA allele-loss (0/N) and allele-loss and duplication (N/N) phenotypes. The frequencies of these erythrocyte variants in the peripheral circulation is a measure of the level of gene-inactivating somatic mutations at the GPA reporter locus in erythroid progenitor cells thus providing an estimate of the acute and cumulative impact of exposure of bone marrow cells to genotoxic agents. Workers were stratified into two exposure categories based on estimated B[a]P levels of <5 ng/m{sup 3} (low exposure group, n=25) and {ge}5 ng/m{sup 3} (high exposure group, n=14). Linear regression analysis revealed significantly elevated frequencies of {O}/N (P=0.025), but not N/N, variants in the high exposure compared to the low exposure group with geometric mean frequency of 13.2 versus 7.9 per million cells, respectively, after adjustment for the effects of age, gender, and smoking status. These data confirm earlier results which suggested a trend toward increased {O}/N variant frequencies associated with greater B[a]P exposures and a significant positive association between the levels of leukocyte PAH-DNA adducts and T-lymphocyte HPRT locus somatic mutations in the peripheral blood of these workers. Taken together, the results demonstrate the power of these biological exposure and effect markers to reveal the impact of low levels of occupational exposure to genotoxic agents such as B[a]P in relatively small populations of workers with well-characterized exposures.
- OSTI ID:
- 530829
- Report Number(s):
- CONF-9704100-; ISSN 0893-6692; CNN: Grant 1 P01 ES05249; TRN: 97:003016-0002
- Journal Information:
- Environmental and Molecular Mutagenesis, Vol. 29, Issue Suppl.28; Conference: 28. annual meeting of the Environmental Mutagen Society, Minneapolis, MN (United States), 19-23 Apr 1997; Other Information: PBD: 1997
- Country of Publication:
- United States
- Language:
- English
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