title: 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. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*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.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University Hospital and Faculty of Medicine in Hradec Kralove, 50005 Hradec Kralove, Czech Republic; Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, 50005 Hradec Kralove, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Beranek
authors.affiliation: Institute of Hygiene and Preventive Medicine, Charles University in Prague, Faculty of Medicine in Hradec Kralove, 50038 Hradec Kralove, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Fiala
authors.affiliation: Institute of Pathological Physiology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, 50038 Hradec Kralove, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kremlacek
authors.affiliation: Institute of Clinical Immunology and Allergology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, 50038 Hradec Kralove, Czech Republic.
authors.forename: Ctirad
authors.initials: C
authors.lastname: Andrys
authors.affiliation: Clinic of Dermal and Venereal Diseases, Charles University Hospital Hradec Kralove, 50005 Hradec Kralove, Czech Republic.
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Hamakova
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University Hospital and Faculty of Medicine in Hradec Kralove, 50005 Hradec Kralove, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Chmelarova
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Charles University Hospital and Faculty of Medicine in Hradec Kralove, 50005 Hradec Kralove, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Palicka
authors.affiliation: Institute of Pathological Physiology, Charles University in Prague, Faculty of Medicine in Hradec Kralove, 50038 Hradec Kralove, Czech Republic. Electronic address: borka@lfhk.cuni.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Borska
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D001711:Biotransformation; D003033:Coal Tar / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D014467:Ultraviolet Therapy; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001564:Benzo(a)pyrene; D003033:Coal Tar; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts; D004851:Epoxide Hydrolases; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D007641:Keratolytic Agents; D000099148:UGT1A1 Enzyme; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; C585496:CYP1B1 protein, human; C522330:EPHX1 protein, human
keywords: BPDE-DNA adducts; Benzo[a]pyrene; Genetic polymorphisms; Psoriasis; Tar