Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis.
BACKGROUND
Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar [polycyclic aromatic hydrocarbons (PAH)] and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis.


METHODS
We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT.


RESULTS
Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P < 0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P < 0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P < 0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P < 0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P < 0.001), confirming clinical benefit of this treatment.


CONCLUSIONS
Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.
Borska
Lenka
L
Institute of Pathological Physiology, Charles University in Prague, Faculty of Medicine, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic. borka@lfhk.cuni.cz
Andrys
Ctirad
C
Krejsek
Jan
J
Hamakova
Kvetoslava
K
Kremlacek
Jan
J
Palicka
Vladimir
V
Ranna
Dianna
D
Fiala
Zdenek
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003033:Coal Tar / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D004249:DNA Damage; D053222:Fas Ligand Protein / Q000097:blood; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D011721:Pyrenes / Q000032:analysis; D012869:Skin Absorption; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D014467:Ultraviolet Therapy / Q000009:adverse effects*; D055815:Young Adult
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D016159:Tumor Suppressor Protein p53; D003033:Coal Tar; C033146:1-hydroxypyrene