GSTM1 [corrected] deletion modifies the levels of polycyclic aromatic hydrocarbon-DNA adducts in human sperm.
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.
Paracchini
Valentina
V
Molecular and Genetic Epidemiology Unit, Palazzina Bertarelli, Fondazione Policlinico IRCCS, Via Pace 9, 20122 Milano, Italy.
Chang
Seong-Sil
SS
Santella
Regina M
RM
Garte
Seymour
S
Pedotti
Paola
P
Taioli
Emanuela
E
D018736:DNA Adducts / Q000378:metabolism*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011110:Polymorphism, Genetic; D013094:Spermatozoa / Q000737:chemistry*
D018736:DNA Adducts; D017931:DNA Primers; D011084:Polycyclic Aromatic Hydrocarbons; D005982:Glutathione Transferase