Genotoxic potential of combined dermal exposure to polycyclic aromatic hydrocarbons and ultraviolet radiation
Abstrakt
Introduction Combined dermal exposure to crude coal tar (CCT) and ultraviolet radiation (UVR) represents one of the most effective therapies of psoriasis (Goeckerman therapy, GT). On the other hand, however, the CCT contains a mixture of polycyclic aromatic hydrocarbons (PAHs) some of them have proven immunosuppressive, mutagenic, genotoxic and carcinogenic effects.
According to International Agency for Research on Cancer (IARC) both components of GT (CCT and UVR wavelengths 100-400 nm, encompassing UVA, UVB, and UVC) were included into group 1 (Carcinogenic to humans). In addition, the results of some studies show that UVR alone or in combination with other common environmental pollutants (including PAHs) could increase photo-damage and risk of skin cancer.
For these reasons, it is currently a debate about the extent of genotoxic hazard/risks of GT. Aim The aim of this study was to contribute to a better understanding of the genotoxic hazard of GT.
Methods The study group of patients suffering from chronic stable plaque psoriasis (n=32, male n=15, smokers n=13, 18 to 69 years, median 53.5, Q1-Q3 34.17-60 years) was treated by GT (4% crude coal tar ointment applied topically and UVB 311 nm whole body irradiation). The heparinized peripheral blood samples were collected into vacuum tubes before the first and immediately after the last procedure.
We used "Cytokinesis-block" micronucleus test (cultivation 72 hours, Cytochalasin B in 44th hour, hypotonic 0.55% KCl solution) and chromosomal aberration assay (cultivation 50 hours, Colcemid in 48th hour, hypotonic 0.55% KCl solution) stained by Giemsa solution. We assessed (1) number and distribution of micronuclei (MN), nuclear buds (gen amplification) and nucleoplasmic bridges (dicentric chromosome) in 1 000 binucleated lymphocytes (BNL) and (2) structural aberration (SAL) and numerical (NAL) aberration in 100 metaphasical lymphocytes.
Results Total number of BNL with MN (p<0.001), BNL with 1 MN (p<0.001), BNL with 2 MN (p<0.05), BNL with GREATER-THAN OR EQUAL TO3 MN (p<0.01), total number of aberrated cells (SAL+NAL; p<0.001) and SAL (p<0.001) were significantly increased after GT. Smokers had significantly higher total number of aberrated cells (p<0.05) and number of smoked cigarettes correlated with total number of aberrated cells before GT (rho=0.38, p<0.05).
We found correlation between age and BNL with MN before GT (rho=0.55, p<0.001) and correlation between range of psoriatic lesions and total number of aberrated cells after GT (r=0.37, p<0.05). PASI score (Psoriasis Area Severity Index) decreased significantly (p < 0.001) after GT.
Discussion According to the literature, no one has yet evaluated the genotoxic potential of GT using by CBMN (MN counts, including nucleoplasmic bridges and nuclear buds). The total number of BNL with MN (mean+-standard deviation; 21.16+-13.84 %o after GT) was similar as in the group of Turkish asphalt workers (21.6+-2.5 %o), lower than in the group of sewage workers in Paris (38.02+-7.16 %o) and higher than in the group of Prague city policemen (7.32+-3.42 %o).
After GT there was increase in BNL with 2 or more MN especially in women. The number of SAL after GT (5.56+-1.92 %) was similar as in the group of Indian coke oven workers (4.6+-1.4%) and Roma airport personnel (4.13 %) but higher than in the group of Prague city policemen (2.07+-1.48 %).
Conclusions/Summary Combined therapeutic exposure to PAHs and UVB induced an increase in the level of the micronuclei and chromosomal aberrations in lymphocytes of psoriatic patients and thus increased the hazard of malignant transformation of blood cells. It can be assumed that a similar situation also occurs in tissues that are intensively supplied with blood.