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
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
27188524
DOI
10.1016/j.toxlet.2016.05.009
PII: S0378-4274(16)30107-2
Knihovny.cz E-resources
- Keywords
- BPDE-DNA adducts, Benzo[a]pyrene, Genetic polymorphisms, Psoriasis, Tar,
- MeSH
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide metabolism MeSH
- DNA Adducts metabolism MeSH
- Administration, Cutaneous MeSH
- Benzo(a)pyrene administration & dosage adverse effects metabolism MeSH
- Biotransformation MeSH
- Cytochrome P-450 CYP1B1 genetics metabolism MeSH
- Coal Tar administration & dosage adverse effects metabolism MeSH
- Adult MeSH
- Epoxide Hydrolases genetics metabolism MeSH
- Pharmacogenetics MeSH
- Phenotype MeSH
- Gene Frequency MeSH
- Glucuronosyltransferase genetics metabolism MeSH
- Glutathione Transferase genetics metabolism MeSH
- Heterozygote MeSH
- Risk Assessment MeSH
- Homozygote MeSH
- Keratolytic Agents administration & dosage adverse effects metabolism MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Polymorphism, Genetic * MeSH
- DNA Damage MeSH
- Psoriasis enzymology genetics therapy MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Ultraviolet Therapy * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide MeSH
- DNA Adducts MeSH
- benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA MeSH Browser
- Benzo(a)pyrene MeSH
- CYP1B1 protein, human MeSH Browser
- Cytochrome P-450 CYP1B1 MeSH
- Coal Tar MeSH
- EPHX1 protein, human MeSH Browser
- Epoxide Hydrolases MeSH
- Glucuronosyltransferase MeSH
- glutathione S-transferase M1 MeSH Browser
- Glutathione Transferase MeSH
- Keratolytic Agents MeSH
- UGT1A1 enzyme MeSH Browser
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.
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