- MeSH
- dějiny lékařství MeSH
- financování zdravotní péče MeSH
- lidé MeSH
- řízení zdravotního stavu populace * MeSH
- veřejné zdravotnictví MeSH
- zdraví * MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Evropa MeSH
Polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) represent genotoxic factors that commonly occur in the living and working environment. The dermal form of exposure represents a significant part of the total load of dangerous chemical and physical environmental factors to which an organism is subjected. However, simultaneous dermal exposures to PAHs (pharmaceutical crude coal tar [CCT]) and UV (UVA and UVB) also have therapeutic uses. A typical example is Goeckerman therapy (GT) for psoriasis. The question of the therapeutic efficacy of GT and the related level of genotoxic danger is still under discussion. The aim of the present study was to compare four GT variants (G1-G4) in terms of efficacy and acceptable genotoxic hazard. Efficacy was expressed by the psoriasis area of severity index (PASI) score, genotoxic hazard by chromosomal aberration in peripheral lymphocytes. The lowest risk of genotoxic hazard and the lowest efficiency was observed in G1 variant (3% of the CCT and UVA + UVB). The efficacy of G2 (4% CCT and UVA + UVB), G3 (4% CCT and UVB), and G4 variants (5% CCT and UVA + UVB) was comparable. The highest risk of genotoxic hazard was found in the G3 variant. In the terms of sufficient efficacy and acceptable genotoxic hazard, a combination of 4% or 5% of CCT and UVA and UVB seems to be acceptable (variants G2 and G4).
- MeSH
- chromozomální aberace MeSH
- dehet uhelný terapeutické užití MeSH
- lidé MeSH
- lymfocyty MeSH
- polycyklické aromatické uhlovodíky toxicita MeSH
- poškození DNA MeSH
- psoriáza farmakoterapie MeSH
- ultrafialové záření * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
(1) Background: Graphene is a two-dimensional atomic structure with a wide range of uses, including for biomedical applications. However, knowledge of its hazards is still limited. This work brings new cytotoxic, cytostatic, genotoxic and immunotoxic data concerning the in vitro exposure of human cell line to two types of graphene platelets (GP). It also contributes to the formation of general conclusions about the health risks of GP exposure. (2) Methods: In vitro exposure of a THP-1 cell line to three concentrations of two GP over 40 h. The cytotoxic potential was assessed by the measurement of LDH and glutathione (ROS) and by a trypan blue exclusion assay (TBEA); the cytostatic and genotoxic potential were assessed by the cytokinesis-block micronucleus (CBMN) test; and the immunotoxic potential was assessed by the measurement of IL-6, IL-10 and TNF-α. (3) Results: We found a significant dose-dependent increase in DNA damage (CBMN). The lowest observed genotoxic effect levels (LOGEL) were 5 µg/mL (GP1) and 30 µg/mL (GP2). We found no significant leaking of LDH from cells, increase in dead cells (TBEA), induction of ROS, increased levels of cytostasis, or changes in IL-6, IL-10 and TNF-α levels. (4) Conclusions: The genotoxicity increased during the short-term in vitro exposure of THP-1 to two GP. No increase in cytotoxicity, immunotoxicity, or cytostasis was observed.
- Publikační typ
- časopisecké články MeSH
Polycyklické aromatické uhlovodíky (PAU) představují skupinu významných kontaminantů pracovního i životního prostředí. Při expozici PAU v pracovním prostředí se vedle inhalační expoziční cesty může významně uplatňovat i expozice dermální. Stávající experimentální údaje o intenzitě a rychlosti penetrace látek do systémové cirkulace jsou zatím omezené. Předkládaný článek se zabývá metodickou a interpretační problematikou transepidermální absorpce PAU in vitro. Byla sledována intenzita (Flux) a rychlost (Lag time) penetrace naftalenu, fenanthrenu, pyrenu a benzo[a]pyrenu přes epidermální membránu z prasečího boltce. Experiment byl prováděn ve vertikálních statických difuzních komůrkách dle Franze (n = 32) a jako rozpouštědlo byl použit isopropyl-myristát. Parametr Flux (nmol/cm2/hod) dosáhl hodnot 95,7 ± 45,5 u naftalenu, 19,5 ± 8,7 u fenanthrenu, 4,38 ± 1,98 u pyrenu a 0,21 ± 0,08 u benzo[a]pyrenu. Parametr Lag time (hod) hodnot 0,26 ± 0,17 u naftalenu, 2,12 ± 0,41 u fenanthrenu, 3,25 ± 0,50 u pyrenu a 11,2 ± 4,08 u benzo[a]pyrenu. Hodnota parametru Flux klesala s molární hmotností PAU, zatímco hodnota parametru Lag time s molární hmotností PAU stoupala. Množství PAU, které za daný časový úsek penetrovalo přes epidermální membránu, se pohybovalo mezi 0,24 % (benzo[a]pyren) až 0,84 % (fenanthren) aplikované dávky. Penetrace PAU přes epidermální membránu vykazovala, v porovnání s experimenty na plné kůži, nižší stupeň variability dat. Z výsledků vyplývá, že použití epidermální membrány by mohlo zpřesňovat jak odhad vnitřní dávky PAU po dermální expozici, tak i odhad souvisejícího zdravotního rizika v rámci konzervativního expozičního scénáře. Experimenty s epidermální membránou jsou však časově i experimentálně náročné, bez možnosti objektivní kontroly integrity epidermální membrány, což může vést k finanční náročnosti testování, ztrátám vzorků a v neposlední řadě i k nárůstu rozdílů hodnot dat, získaných v různých laboratořích.
Polycyclic aromatic hydrocarbons (PAHs) are a group of significant contaminants in the occupational and living environment. In addition to the inhalation route of exposure in the occupational environment, there is also significant the dermal route of exposure. Existing experimental data on the intensity and rate of penetration of these substances into systemic circulation are still limited. The presented paper is focused on methodological and interpretative issues of trans-epidermal absorption of PAHs in vitro. In this study, we assessed the intensity (Flux) and rate (Lag time) of penetration of naphthalene, phenanthrene, pyrene and benzo[a]pyrene through the epidermal membrane derived from a pig ear. The experiment was performed using static vertical Franz diffusion cells (n = 32) and isopropyl myristate was used as a solvent. Flux (nmol/cm2/hour) reached 95.7 ± 45.5 in the case of naphthalene, 19.5 ± 8.7 of phenanthrene, 4.38 ± 1.98 of pyrene and 0.21 ± 0.08 of benzo[a]pyrene. Lag time (hour) was 0.26 ± 0.17 in the case of naphthalene, 2.12 ± 0.41 of phenanthrene, 3.25 ± 0.50 of pyrene and 11.2 ± 4.08 of benzo[a]pyrene. The Flux value decreased with the molecular weight of PAHs, while the Lag time increased with the molecular weight of PAHs. The amount of PAHs that penetrated through the epidermal membrane in a given time period ranged between 0.24% (benzo[a]pyrene) and 0.84% (phenanthrene) of the applied dose. The penetration of PAHs through the epidermal membrane showed a lower degree of data variability compared to full thickness skin experiments. The results suggest that the use of the epidermal membrane could define more accurately both the estimation of the internal dose of PAHs after dermal exposure and the estimation of the associated health risk within a conservative exposure scenario. However, experiments with using the epidermal membrane are time consuming and experimentally demanding, with no option of an objective control of the integrity of the epidermal membrane, which can lead to costly testing, loss of samples and, finally, an increase in the differences in data values obtained in different laboratories.
- MeSH
- epidermis anatomie a histologie patofyziologie MeSH
- interpretace statistických dat MeSH
- kožní absorpce * fyziologie MeSH
- modely u zvířat MeSH
- polycyklické aromatické uhlovodíky * škodlivé účinky MeSH
- prasata MeSH
- techniky in vitro * metody statistika a číselné údaje MeSH
- ušní boltec MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
AIMS: Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. METHODS: The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. RESULTS: The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3.4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. CONCLUSION: The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.
- MeSH
- chromozomální aberace účinky léků účinky záření MeSH
- chronická nemoc MeSH
- dehet uhelný škodlivé účinky MeSH
- dospělí MeSH
- dvouřetězcové zlomy DNA účinky léků účinky záření MeSH
- keratolytika škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty * MeSH
- psoriáza terapie MeSH
- senioři MeSH
- terapie ultrafialovými paprsky škodlivé účinky MeSH
- ultrafialové záření škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
