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Methoxsalen

Methoxsalen (marketed under the trade name oxsoralen) is a drug used to treat psoriasis in conjunction with exposing the skin to sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10mg tablets, which are taken in the amount of 30mg 75 minutes before a PUVA light treatment. more...

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Patients with high blood pressure or a history of liver problems are at risk for inflammation and irreparable damage to both liver and skin. The eyes must be protected from UVA radiation. Side effects include nausea, headaches, dizziness, and in rare cases insomnia.

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High mutation frequency at Ha-ras exons 1-4 in squamous cell carcinomas from PUVA-treated psoriasis patients
From Photochemistry and Photobiology, 8/1/01 by Kreimer-Erlacher, Heidemarie

High Mutation Frequency at Ha-ras Exons 1-4 in Squamous Cell Carcinomas from PUVA-treated Psoriasis Patients

ABSTRACT

Clinical follow-up studies have revealed that PUVA-- treated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (ie. C-->T or CC-->TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C->T transitions), five (28%) were at 5'-TpG sites (ie. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C-->T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A-4C:G base change at codon 27 (a 5'-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients.

^Abbreviations: GDP, guanosine diphosphate; GTP, guanosine triphosphate; HPV, human papillomavirus; MOP, methoxypsoralen; PCR, polymerase chain reaction; PUVA, psoralen and UVA; SCC, squamous cell carcinoma; SSCP, single-strand conformation polymorphism.

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Heidemarie Kreimer-Erlacher, Hannes Seidl, Barbara Back, Helmut Kern and Peter Wolf*

Department of Dermatology, Karl-Franzens University, Graz, Austria

Received 4 January 2001; accepted 5 May 2001

(par)Posted on the website on 8 June 2001.

*To whom correspondence should be addressed at: Department of Dermatology, Karl-Franzens University, Auenbrugger Platz 8, A-- 8036 Graz, Austria. Fax: 43-316-385-2466; e-mail: peter.wolf@kfunigraz.ac.at

Copyright American Society of Photobiology Aug 2001
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