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PRESENTED AT COPENHAGEN WORKSHOP ON ENVIRONMENTAL, REPRODUCTIVE HEALTH AND FERTILITY, COPENHAGEN, DENMARK, 1/15-18/2005: GST M1 GENOTYPE INFLUENCES SPERM DNA DAMAGE ASSOCIATED WITH EXPOSURE TO AIR POLLUTION
Citation:
DARNEY, S. P., S. G. SELEVAN, R. SRAM, D. P. EVENSON, AND J. RUBES. PRESENTED AT COPENHAGEN WORKSHOP ON ENVIRONMENTAL, REPRODUCTIVE HEALTH AND FERTILITY, COPENHAGEN, DENMARK, 1/15-18/2005: GST M1 GENOTYPE INFLUENCES SPERM DNA DAMAGE ASSOCIATED WITH EXPOSURE TO AIR POLLUTION. Presented at Copenhagen Workshop on Environmental, Reproductive Health and Fertility, Copenhagen, DENMARK, January 15 - 18, 2005.
Description:
Exposure to episodic air pollution in the Czech Republic has been associated with abnormal semen quality and sperm DNA damage (EHP 108:887;2000). A subsequent longitudinal study evaluated semen from 36 men sampled up to 7 times over a period of two years to capture exposures during both low and high air pollution. As before, exposure was significantly associated with increased DNA fragmentation index (DFI) as detected by the Sperm Chromatin Structure Assay. Formation of DNA adducts in sperm with exposure to metabolites of polycyclic aromatic hydrocarbons (PAHs) in air pollution is biologically plausible. Because PAH metabolites are detoxified by glutathione s-transferase M1, we hypothesized that men lacking the gene for this enzyme, GST M1(-), might be more susceptible to effects of air pollution on sperm DNA. To test this, GST M1 genotyping was performed. As expected, about half of the men were GST M1(-).The relationship between pollution and DFI was then re-examined with and without genotype in the model, adjusted for smoking. For exposure and DFI (without genotype), (95% CL) = 0.175 (0.006, 0.345); for genotype and DFI (without exposure), ? = 0.251 (0.030, 0.473); and, for the interaction (exposure x genotype) and DFI, ? = 0.427 (0.157, 0.697). Although DFI was associated with both exposure and genotype, the interaction between genotype and exposure was even more significant. This novel gene-environment interaction supports the hypothesis that GST M1(-) men may be at increased risk for sustaining DNA damage in their sperm and may be more susceptible than GST M1 men to adverse reproductive effects of air pollution.
Supported by US EPA R820968 and CR Ministry of Environment VaV/340/02/00. This abstract does not reflect EPA policy.