p53 Mutation in Squamous Cell Carcinomas from Psoriasis Patients Treated with Psoralen + UVA (PUVA)

Individuals suffering from psoriasis are treated with a combination of psoralen and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies have shown that PUVA therapy is a risk factor for skin cancer in psoriasis patients. Although PUVA treatment induces skin cancer in laboratory animals, it is unknown whether the increased incidence of skin cancer reported in PUVA-treated psoriasis patients is due to the carcinogenic effects of PUVA or due to other factors such as UVB. Because CV and PUVA induce different types of DNA damage resulting in unique types of p53 mutation, we investigated whether skin cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53 mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA-treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of p53 mutations occurred at 5'TpG sites. Although previous studies have shown that 5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG sites are also quite common. Interestingly, a sizable portion of p53 mutations detected were C→T or CC→TT transitions, characteristic of UV-induced mutations. Because some psoriasis patients had substantial exposure to UVB before PUVA therapy and because the light sources used in PUVA therapy contained small but significant wave-lengths in the UVB region, it is possible that the C→T and CC→TT transitions detected in SCCs from PUVA-treated patients were induced by UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in the development of skin cancer in Austrian psoriasis patients who undergo PUVA therapy

Fate of UVB-induced p53 mutations in SKH-hr1 mouse skin after discontinuation of irradiation: relationship to skin cancer development

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The marine biology of law and human health

© Marine Biological Association of the United Kingdom 2015. This review uses a multidisciplinary approach to investigate legal issues concerning the oceans and human health. It firstly seeks to define the boundaries of oceans and human health research. We use three case studies as examples: biomedical research, marine litter and human well-being. Biomedical research raises complex issues relating to coastal states' sovereign rights to exploit their marine resources and the patenting processes. Coastal states have differing degrees of control over research at sea. There are differences in EU and US law over the status of genetic discoveries, with the US having stricter criteria to qualify for patent protection. International law sets the standard for bioprospecting in developing countries under the Nagoya Protocol. The cost and complexity of marine biomedical research mean that it cannot be left to commercial exploration and needs some public funding. The second case study highlights the rise in marine plastics pollution using Marine Conservation Society beachwatch data. It details the need to alter product design to avoid marine pollution and records an unsuccessful attempt by academics and an NGO to make contact with the manufacturers of one polluting product. It also introduces the concept that faulty design could amount to a public nuisance. The third case study highlights the potential health benefits from access to the coast and the statutory responsibility which sits with the US and UK authorities in the provision of well-being. It posits that there needs to be greater inter-agency coordination to promote access to the coast for human well-being

Ion association and solvation behavior of nicotinium dichromate in water-N,N-dimethyl formamide mixtures by a conductometric study

The electrical conductance of nicoitinium dichromate has been measured in water-N,N-dimethyl formamide mixtures of different compositions in the temperature range 283-313 K. The limiting molar conductance, Lo and the association constant of the ion-pair, KA have been calculated using Shedlovsky equation. The effective ionic radii (ri) of (C6H6O2)+ and (C6H6O2NCr2O7)- ions have been determined from Lio values using Gill’s modification of the Stokes law. The influence of the mixed solvent composition on the solvation of ions has been discussed with the help of ‘R’-factor. Thermodynamic parameters are evaluated and reported. The results of the study have been interpreted in terms of ion-solvent interactions and solvent properties

Alternative methods to evaluate the protective ability of sunscreen against photo-genotoxicity

Numerous epidemiological investigations show that sunlight is carcinogenic to humans and that the use of sunscreen may be effective in decreasing the risk of skin cancer. The biological activity of a sunscreen is evaluated by its ability to protect human skin from erythema as represented by a Sun Protection Factor (SPF). We propose that the sunscreen's protective effect against sunlight-induced genotoxicity, including mutation, should also be taken into account. In this study we examined the protective ability of sunscreens against natural sunlight and UV-induced genotoxicity in Drosophila somatic cells. We prepared three kinds of sunscreen samples, each with an SPF value of 20, 40 or 60 and compared their protective activities with commercial sunscreens. When a sunscreen of SPF 20, 40 or 60 was pasted on the plastic cover of a petri dish in which Drosophila larvae were exposed to the sun or UV lamps, genotoxicity decreased as the SPF of the sunscreen increased, relative to levels of genotoxicity observed in samples without sunscreen. However, the protective abilities of sunscreens were unexpectedly not so different from each other. To reveal the relationship between the protective activity of sunscreen and the wavelength of light with which larvae were irradiated through the sunscreen, we measured the transmittance of light through the petri dish cover on which the sunscreen was pasted. Effective protection was demonstrated by removing components of light whose wavelengths were below 315 nm. We suggest, that the measurement of anti-genotoxic activity and the determination of the wavelengths of light transmitted through the sunscreen should be an alternative method for evaluating the effectiveness of a sunscreen.</p

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA\u27s mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects