Myeloperoxidase--463A variant reduces benzo[a]pyrene diol epoxide DNA adducts in skin of coal tar treated patients
| Jazyk: | English |
|---|---|
| ISSN: | 0143-3334 |
| DOI: | 10.1093/carcin/22.7.1015 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ad17b067b131350f18066806974ad4f https://doi.org/10.1093/carcin/22.7.1015 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....0ad17b067b131350f18066806974ad4f |
| Autor: | Ingolf Cascorbi, Frederik-Jan van Schooten, Roger W. L. Godschalk, E. Kriek, Margarita Rojas, Kroum Alexandrov, Judith Ostertag, Helmut Bartsch |
| Přispěvatelé: | Gezondheidsrisico Analyse en Toxicologie, Dermatologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Cancer Research Adolescent 7 8-Dihydro-7 8-dihydroxybenzo(a)pyrene 9 10-oxide Diol Epoxide Human skin High-performance liquid chromatography Adduct DNA Adducts chemistry.chemical_compound polycyclic compounds Humans Biotransformation Coal Tar Peroxidase Skin Polymorphism Genetic biology DNA General Medicine Middle Aged Molecular biology chemistry Biochemistry Benzo(a)pyrene Myeloperoxidase biology.protein Pyrene Female Mutagens |
| Zdroj: | Carcinogenesis, 22, 1015-1018. Oxford University Press |
| ISSN: | 0143-3334 |
| DOI: | 10.1093/carcin/22.7.1015 |
| Popis: | Carcinogenesis 2001 Jul;22(7):1015-8 Related Articles, Books, LinkOut Myeloperoxidase--463A variant reduces benzo[a]pyrene diol epoxide DNA adducts in skin of coal tar treated patients.Rojas M, Godschalk R, Alexandrov K, Cascorbi I, Kriek E, Ostertag J, Van Schooten FJ, Bartsch H.German Cancer Research Center (DKFZ), Division of Toxicology and Cancer Risk Factors, PO Box 101949, D-69009 Heidelberg, Germany.The skin of atopic dermatitis patients provides an excellent model to study the role of inflammation in benzo[a]pyrene (BaP) activation, since these individuals are often topically treated with ointments containing high concentrations of BaP. In this study we have determined, by HPLC with fluorescence detection, the BaP diol epoxide (BPDE)-DNA adduct levels in human skin after topical treatment with coal tar and their modulation by the -463G-->A myeloperoxidase (MPO) polymorphism, which reduces MPO mRNA expression. BPDE-DNA adduct levels were 2.2 and 14.2 adducts/10(8) nt for MPO-463AA/AG and -463GG, respectively. The predominant BaP tetrol observed was tetrol I-1, which is derived after hydrolysis of the anti-BPDE-DNA adduct. The tetrol I-1/II-2 ratio, corresponding to the anti/syn ratio, was 6.7. The (32)P-post-labeling assay was also performed and thin layer chromatograms showed a major spot with a chromatographic location corresponding to BPDE-DNA. The mean values of the BPDE-DNA adduct spots were 3.8 +/- 2.4 per 10(8) nt for MPO-463AA/AG (n = 3) and 18.4 +/- 11.0 per 10(8) nt for MPO-463GG (n = 7), respectively (P = 0.03). One individual with the homozygous mutant genotype (-463AA) even had a 13-fold lower adduct level (1.4 per 10(8) nt) as compared to MPO-463GG subjects. In conclusion, these data show for the first time: (i) the in vivo formation of BPDE-DNA adducts in human skin treated with coal tar; (ii) that the MPO-463AA/AG genotype reduced BPDE-DNA adduct levels in human skin. |
| Databáze: | OpenAIRE |
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