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

• Published in: Toxicology letters Vol. 255; pp. 47 - 51
• Main Authors: Beranek, Martin, Fiala, Zdenek, Kremlacek, Jan, Andrys, Ctirad, Hamakova, Kvetoslava, Chmelarova, Marcela, Palicka, Vladimir, Borska, Lenka
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.07.2016
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - metabolism; Adducts; Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Benzo(a)pyrene - administration & dosage; Benzo(a)pyrene - adverse effects; Benzo(a)pyrene - metabolism; Benzo[a]pyrene; Biotransformation; BPDE-DNA adducts; Coal tar; Coal Tar - administration & dosage; Coal Tar - adverse effects; Coal Tar - metabolism; Cytochrome P-450 CYP1B1 - genetics; Cytochrome P-450 CYP1B1 - metabolism; Deoxyribonucleic acid; DNA Adducts - metabolism; DNA Damage; Droplets; Epoxide Hydrolases - genetics; Epoxide Hydrolases - metabolism; Female; Fragmentation; Gene Frequency; Genetic polymorphisms; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Heterozygote; Homozygote; Humans; Keratolytic Agents - administration & dosage; Keratolytic Agents - adverse effects; Keratolytic Agents - metabolism; Male; Middle Aged; Patients; Pharmacogenetics; Phenotype; Polymorphism; Polymorphism, Genetic; Psoriasis; Psoriasis - enzymology; Psoriasis - genetics; Psoriasis - therapy; Real-Time Polymerase Chain Reaction; Risk Assessment; Tar; Therapy; Ultraviolet Therapy; Young Adult; BPDE-DNA adducts; Benzo[a]pyrene; Tar; Psoriasis; Genetic polymorphisms
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2016.05.009

•Goeckerman therapy of psoriasis includes exposure to benzo[a]pyrene.•Benzo[a]pyrene creates benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA (BPDE-DNA) adducts.•The therapy increases the level of BPDE-DNA adducts.•The level of DNA adducts was highest in CYP1B1*1/*1 and EPHX1*1/*1 wild-type subjects.•CYP1B1/EPHX1 genotyping could help to predict individual sensitivity to DNA damage. 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.