DNA interstrand crosslinks visualized by electron microscopy in PUVA-treated psoriasis

Area of Science:

• Dermatology
• Molecular Biology
• Genetics

Background:

• Psoriasis is a chronic inflammatory skin condition.
• Photochemotherapy, specifically PUVA (psoralen plus UVA light), is a common treatment for psoriasis.
• 8-methoxypsoralen (8-MOP) is a photosensitizing agent used in PUVA therapy.

Purpose of the Study:

• To investigate the formation of DNA interstrand crosslinks in patients with psoriasis undergoing PUVA treatment.
• To quantify the number and density of DNA crosslinks in both epidermal and dermal cells after PUVA therapy.
• To compare DNA crosslink frequencies between topical and systemic 8-MOP treatments.

Main Methods:

• Electron microscopy was employed to visualize and measure DNA interstrand crosslinks after total DNA denaturation.
• 30 biopsies from psoriasis patients treated with 8-MOP and UVA irradiation were analyzed.
• A total of 9503 DNA molecules were scored to determine crosslink frequency.

Main Results:

• The frequency of DNA molecules with three or more crosslinks was 1%.
• DNA crosslink frequencies were similar in both epidermis (1.1%) and dermis (0.9%).
• No significant difference in crosslink frequency was observed between topical and systemic PUVA treatments, nor compared to normal human skin.

Conclusions:

• PUVA treatment with 8-MOP did not demonstrably increase the formation of DNA interstrand crosslinks in psoriasis patients.
• While DNA crosslinks can indicate genetic damage, this study did not find them to be a consequence of 8-MOP-based PUVA therapy.
• The findings suggest that PUVA treatment, as assessed by DNA crosslink formation, does not cause significant genetic damage in the treated skin.