PubMed · 14890399
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J P D'ORS. [Therapeutic progress].. https://pubmed.ncbi.nlm.nih.gov/14890399/
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The equilibrium distributions, between water and coal-tar contaminated sediment, of 16 monocyclic and polycyclic aromatic hydrocarbons were measured and evaluated for consistency with a Raoult's Law-based quantitative relationship. The quantitative relationship calculates the pore water concentration as the product of the aqueous solubility (or for compounds that are solid at room temperature, the aqueous super-cooled liquid solubility) and the mole fraction concentration of the compound within the liquid coal tar. Sediment was collected at five locations at two depths within a 120 m stretch of a river adjacent to a former manufactured gas plant, and all samples contained non-aqueous phase liquid (NAPL) coal tar. Although the amount of coal tar varied between samples by over an order of magnitude, the Raoult's Law-based NAPL-water partition coefficients for each monocyclic or 2- or 3-ring polycyclic aromatic hydrocarbon measured in this study generally varied within a factor of 2 over all sediments.
Hazard assessment of industrial sites contaminated with coal tar and its products usually focuses on selected pollutants such as the 16 polycyclic aromatic hydrocarbons (PAHs) prioritized by the U.S. Environmental Protection Agency (U.S. EPA). The aim of this study was to investigate to which extent these 16 PAHs contribute to the Vibrio fischeri bioluminescence inhibition measured by the acute Lumistox luminescent bacteria test. Five of the 16 PAHs-naphthalene (NAP), acenaphthylene (ACY), acenaphthene (ACE), fluorene (FLU), and phenanthrene (PHE)-revealed inhibiting effects when measuring saturated aqueous solutions of these compounds. However, in elutriates of PAH-contaminated soils, the amount of leached PAHs was very low, and the 16 PAHs did not considerably contribute to the observed bioluminescence inhibition. Nevertheless, bioluminescence inhibition was higher for elutriates with increased PAH concentration indicating the presence of other toxicants that co-occur with the 16 PAHs. No evidence was observed for increased bioluminescence inhibition due to synergistic effects among PAHs as calculated on the basis of toxic units for an aqueous solution containing all 16 priority PAHs. Data suggest that the U.S. EPA PAHs play only a minor role in causing acute toxicity to V. fischeri when exposed to aqueous elutriates of PAH-contaminated soils.
BACKGROUND: Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. METHODS: We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. FINDINGS: We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. INTERPRETATION: These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.