Oxidative Damage to Nucleic Acids and Benzo(a)pyrene-7,8-diol-9,10-epoxide-DNA Adducts and Chromosomal Aberration in Children with Psoriasis Repeatedly Exposed to Crude Coal Tar Ointment and UV Radiation

Abstract

The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).

Serum Level of Antibodies (IgG, IgM) Against Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA Adducts in Children Dermatologically Exposed to Coal Tar

“…Monitored groups consisted of patients (men, women, and children) suffering from psoriasis treated by GT. In the groups of children, we found high degree of dermal absorption of PAHs (elevated levels of urinary 1-hydroxypyrene and hydroxylated phenanthrenes), elevated urinary mutagenicity (Ames test), and increased genotoxicity (chromosomal aberration in peripheral lymphocytes) (8,10,11). In addition, we found an elevated level of cellular stress (heat shock proteins; Hsp70) (11), oxidative stress (8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine and 8-hydroxyguanine), and BPDE-DNA adducts (8).…”

“…Basic characteristics of the study group were described in our previous work (8). Briefly, the group was formed of children with chronic stable plaque psoriasis, treated by GT at the Clinic of Dermal and Venereal Diseases, University Hospital, Hradec Králové (Czech Republic).…”

“…Detailed treatment procedure and the content of 16 selected PAHs in dermatological CCT were described previously (8). The therapy was based on daily application of dermatological ointment, containing 3% of CCT.…”

“…The therapy combines dermal exposure of crude coal tar (CCT) ointment and UV radiation (UVR) (7)(8)(9)(10)(11)(12). It seems that fundamental mechanism of therapeutic effects of CCT is based on immunosuppression induced by polycyclic aromatic hydrocarbons in coal tar (PAHs) without signs of systemic immuno-toxicity (9,12).…”

“…It seems that fundamental mechanism of therapeutic effects of CCT is based on immunosuppression induced by polycyclic aromatic hydrocarbons in coal tar (PAHs) without signs of systemic immuno-toxicity (9,12). Retrospective studies have demonstrated that GT is effective in children and adolescents with moderate to severe psoriasis (7)(8)(9)(10)(11)(12). However, the use of GT has recently decreased for several reasons, including a supposed genotoxicity of CCT/PAHs (13)(14).…”