TY - JOUR
T1 - GSMT1 deletion modifies the levels of polycyclic aromatic hydrocarbon-DNA adducts in human sperm
AU - Paracchini, Valentina
AU - Chang, Seong Sil
AU - Santella, Regina M.
AU - Garte, Seymour
AU - Pedotti, Paola
AU - Taioli, Emanuela
PY - 2005/10/3
Y1 - 2005/10/3
N2 - DNA adducts measured in tissues are promising markers for identifying damage in organs that could be a target for carcinogens. Polymorphisms in genes involved in polycyclic aromatic hydrocarbons (PAHs) metabolism have been shown to modify the levels of PAH-DNA adducts in target tissues. In order to study the role of metabolic gene polymorphisms on DNA-adduct formation in sperm, we determined the GSTM1 genotype in a group of men in whom PAH-DNA adducts in sperm had been previously measured by immunofluorescence. The mean level of adducts in sperm was significantly higher in subjects carrying the homozygous deletion variant of GSTM1 than in subjects with a functional GSTM1 (mean fluorescence staining intensity: 1.62 ± 0.62 versus 1.33 ± 0.55; p = 0.02). With respect to environmental factors, subjects who reported occupational exposure to PAHs and who carried the GSTM1 deletion had a significant increase in PAH-DNA adducts in sperm in comparison with subjects who were not exposed and had a functional GSTM1 (mean staining intensity: 1.83 ± 0.67 versus 1.30 ± 0.53; p = 0.05), although among GSTM1-null subjects there was no significant difference with or without occupational exposure. This study presents for the first time the effect of a common polymorphism in a gene that metabolizes PAHs on DNA-adduct levels in sperm.
AB - DNA adducts measured in tissues are promising markers for identifying damage in organs that could be a target for carcinogens. Polymorphisms in genes involved in polycyclic aromatic hydrocarbons (PAHs) metabolism have been shown to modify the levels of PAH-DNA adducts in target tissues. In order to study the role of metabolic gene polymorphisms on DNA-adduct formation in sperm, we determined the GSTM1 genotype in a group of men in whom PAH-DNA adducts in sperm had been previously measured by immunofluorescence. The mean level of adducts in sperm was significantly higher in subjects carrying the homozygous deletion variant of GSTM1 than in subjects with a functional GSTM1 (mean fluorescence staining intensity: 1.62 ± 0.62 versus 1.33 ± 0.55; p = 0.02). With respect to environmental factors, subjects who reported occupational exposure to PAHs and who carried the GSTM1 deletion had a significant increase in PAH-DNA adducts in sperm in comparison with subjects who were not exposed and had a functional GSTM1 (mean staining intensity: 1.83 ± 0.67 versus 1.30 ± 0.53; p = 0.05), although among GSTM1-null subjects there was no significant difference with or without occupational exposure. This study presents for the first time the effect of a common polymorphism in a gene that metabolizes PAHs on DNA-adduct levels in sperm.
KW - DNA damage
KW - Metabolic genes
KW - Molecular epidemiology
KW - Target tissues
KW - Translational studies
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U2 - 10.1016/j.mrgentox.2005.06.008
DO - 10.1016/j.mrgentox.2005.06.008
M3 - Article
C2 - 16105747
AN - SCOPUS:28644441182
VL - 586
SP - 97
EP - 101
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
SN - 1383-5718
IS - 2
ER -