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.
|Titolo:||GSTM1 [corrected] deletion modifies the levels of polycyclic aromatic hydrocarbon-DNA adducts in human sperm|
PEDOTTI, PAOLA SARA (Penultimo)
|Parole Chiave:||DNA damage; Metabolic genes; Molecular epidemiology; Target tissues; Translational studies|
|Data di pubblicazione:||3-ott-2005|
|Digital Object Identifier (DOI):||10.1016/j.mrgentox.2005.06.008|
|Appare nelle tipologie:||01 - Articolo su periodico|