Coal tar therapy does not influence in vitro benzo[a]pyrene metabolism and DNA adduct formation in peripheral blood lymphocytes of psoriatic patients.
Human lymphocytes (HL) from healthy subjects and psoriatic patients were treated in vitro for 24 h with 4 microM [3H]benzo[a]pyrene (B[a]P) and 2 microM (-)-B[a]P-7,8-dihydrodiol in order to verify if the coal tar (CT) used in the therapy of psoriasis, which is characterized by a high content of polycyclic aromatic hydrocarbons (PAH), influences the formation of B[a]P-DNA adducts and the metabolism of B[a]P. Significant amounts of syn-BPDE-dGuo adducts were detected in all the examined HL samples, but no significant difference in the amounts of total BPDE-DNA adducts or of specific anti- and syn-BPDE-dGuo adducts was observed between healthy subjects and psoriatic patients, or between psoriatic patients before and after CT treatment. Moreover, the CT treatment of psoriatic patients did not influence the enantiomeric composition of B[a]P-7,8-dihydrodiols present in the HL culture medium, among which the (-)-7R,8R form was found to predominate (greater than 98%) in all the HL samples. The existence in HL of a specific metabolic pathway of B[a]P leading to the formation of (-)-syn-BPDE and the corresponding tetrols, through the epoxidation of the (-)-7R,8R enantiomer of B[a]P-7,8-dihydrodiol, was confirmed by determining the tetrols derived from the syn- and anti-stereoisomers of BPDE, released in HL culture medium after treatment for 24 h with 2 microM (-)-B[a]P-7,8-dihydrodiol. Although B[a]P-7,10/8,9 and B[a]P-7/8,9,10 tetrols, derived from (+)-anti-BPDE, were the predominant isomers, significant amounts of B[a]P-7,9/8,10 and B[a]P-7,9,10/8 tetrols, derived from the hydrolysis of (-)-syn-BPDE, were also detected. The mean ratio of anti/syn tetrols in healthy subjects was significantly lower than in psoriatic patients, but no difference in that ratio was found in psoriatic patients before and after CT treatment.
Pavanello
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S
Department of Biology, University of Padova, Italy.
Levis
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AG
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism / Q000633:toxicity; D000328:Adult; D000368:Aged; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D002478:Cells, Cultured; D003033:Coal Tar / Q000627:therapeutic use*; D004249:DNA Damage; D004347:Drug Interactions; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D013237:Stereoisomerism
D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003033:Coal Tar