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Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells

2000; Wiley; Volume: 35; Issue: 2 Linguagem: Inglês

10.1002/(sici)1098-2280(2000)35

1098-2280

Dorota Butkiewicz, Ewa Grzybowska, David H. Phillips, Kari Hemminki, M Choraźy,

Glutathione Transferases and Polymorphisms

Environmental and Molecular MutagenesisVolume 35, Issue 2 p. 99-105 Research Article Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells Dorota Butkiewicz, Corresponding Author Dorota Butkiewicz dorotab@rocketmail.com Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandDepartment of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Ul. Wybrzeże Armii Krajowej 15, 44-101 Gliwice, PolandSearch for more papers by this authorEwa Grzybowska, Ewa Grzybowska Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandSearch for more papers by this authorDavid H. Phillips, David H. Phillips Section of Molecular Carcinogenesis, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey, United KingdomSearch for more papers by this authorKari Hemminki, Kari Hemminki Department of Biosciences, Karolinska Institute, Huddinge, SwedenSearch for more papers by this authorMieczysław Chorąży, Mieczysław Chorąży Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandSearch for more papers by this author Dorota Butkiewicz, Corresponding Author Dorota Butkiewicz dorotab@rocketmail.com Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandDepartment of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Ul. Wybrzeże Armii Krajowej 15, 44-101 Gliwice, PolandSearch for more papers by this authorEwa Grzybowska, Ewa Grzybowska Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandSearch for more papers by this authorDavid H. Phillips, David H. Phillips Section of Molecular Carcinogenesis, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey, United KingdomSearch for more papers by this authorKari Hemminki, Kari Hemminki Department of Biosciences, Karolinska Institute, Huddinge, SwedenSearch for more papers by this authorMieczysław Chorąży, Mieczysław Chorąży Department of Tumor Biology, Centre of Oncology, M. Skłodowska-Curie Memorial Institute, Gliwice, PolandSearch for more papers by this author First published: 09 March 2000 https://doi.org/10.1002/(SICI)1098-2280(2000)35:2 3.0.CO;2-2Citations: 61AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Glutathione S-transferases (GSTs) are an important part of the protection system against a wide range of potentially harmful chemical compounds. GSTP1 and GSTM1 are mainly involved in detoxification reactions of PAH carcinogenic intermediates produced by cytochrome P450 (CYP). Polymorphism of the GST genes may influence the level of carcinogen-DNA adducts in human tissues and be associated with individual susceptibility to carcinogens. In this study, we examined the effect of common polymorphism in exon 5 (105Ile → Val) of the GSTP1 gene, alone and in combination with GSTM1-deletion polymorphism, on the level of PAH-DNA adducts measured by 32P-postlabeling assay in mononuclear white blood cells collected in winter and in summer from a total of 170 healthy volunteers. When GSTP1 genotypes alone were compared, no statistically significant differences in adduct levels were found. However, smokers with GSTM1(null)/GSTP1-AG or -GG combined genotype showed significantly higher adduct levels in summer than carriers of other GSTM1/GSTP1 combinations (5.60 ± 5.10 vs. 3.45 ± 4.28/108 nucleotides, P = 0.015). Among smokers carrying GSTP1-AG or -GG genotype, individuals with GSTM1(null) genotype had a significantly higher level of adducts in summer than subjects with GSTM1(+) genotype (5.60 ± 5.10 vs. 1.82 ± 1.98/108, P = 0.002) and GSTM1(null)/GSTP1-AA genotype carriers (5.60 ± 5.10 vs. 4.13 ± 5.84/108, P = 0.03). When adduct levels measured either in winter or in the nonsmoker group were considered, no influence of GSTM1/GSTP1 genotypes was found. Our data show that the combined GSTM1 and GSTP1 genetic polymorphisms may modulate PAH-DNA adduct levels in mononuclear WBCs from individuals exposed to specific carcinogenic compounds, e.g., tobacco smoke, in relatively lower-exposure environmental conditions (i.e., in summer). Environ. Mol. Mutagen. 35:99–105, 2000 © 2000 Wiley-Liss, Inc. Citing Literature Volume35, Issue22000Pages 99-105 RelatedInformation