Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

Abstract	Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B11/1 wild-type subjects and CYP1B13/1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B13/3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX13/1 heterozygosity revealed fewer adducts than EPHX11/1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.
Authors	Martin Beranek, Zdenek Fiala, Jan Kremlacek, Ctirad Andrys, Kvetoslava Hamakova, Marcela Chmelarova, Vladimir Palicka, Lenka Borska
Journal	Toxicology letters (Toxicol Lett) Vol. 255 Pg. 47-51 (Jul 25 2016) ISSN: 1879-3169 [Electronic] Netherlands
PMID	27188524 (Publication Type: Journal Article)
Copyright	Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Chemical References	DNA Adducts Keratolytic Agents benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA Benzo(a)pyrene 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide Coal Tar CYP1B1 protein, human Cytochrome P-450 CYP1B1 UGT1A1 enzyme Glucuronosyltransferase Glutathione Transferase glutathione S-transferase M1 Epoxide Hydrolases EPHX1 protein, human
Topics	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide (metabolism) Administration, Cutaneous Adult Aged Aged, 80 and over Benzo(a)pyrene (administration & dosage, adverse effects, metabolism) Biotransformation Coal Tar (administration & dosage, adverse effects, metabolism) Cytochrome P-450 CYP1B1 (genetics, metabolism) DNA Adducts (metabolism) DNA Damage Epoxide Hydrolases (genetics, metabolism) Female Gene Frequency Glucuronosyltransferase (genetics, metabolism) Glutathione Transferase (genetics, metabolism) Heterozygote Homozygote Humans Keratolytic Agents (administration & dosage, adverse effects, metabolism) Male Middle Aged Pharmacogenetics Phenotype Polymorphism, Genetic Psoriasis (enzymology, genetics, therapy) Real-Time Polymerase Chain Reaction Risk Assessment Ultraviolet Therapy Young Adult

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