Multiple large surface photodynamic therapy sessions with topical methylaminolaevulinate in PTCH heterozygous mice.
BACKGROUND
Photodynamic therapy (PDT) combines the administration of a photosensitizer with its subsequent activation by light of the appropriate wavelength. Methylaminolaevulinate (MAL) is a photosensitizer precursor, transformed by cells into protoporphyrin IX. The PTCH gene plays a central role in the genesis of basal cell carcinoma (BCC). The PTCH transgenic mouse develops microscopic BCCs when chronically exposed to ultraviolet (UV) or ionizing radiation.


OBJECTIVE
The aim of this study was to explore the ability of multiple large surface MAL-PDT to prevent BCC, using the PTCH heterozygous mouse as a model.


METHODS
Thirty-five mice were exposed to UV radiation for a total of 20 weeks. Group 1 (20 mice) was exposed only to UV whereas group 2 (15 mice) was exposed to UV and weekly to MAL-PDT. At 28 weeks the mice were killed and the skin of the back processed for standard histopathology. Assessment was blind and any slide showing the presence of BCC was counted as a single BCC. The number of mice in groups 1 and 2 showing BCC were compared using Fisher's exact test.


RESULTS
Nineteen BCCs in nine mice from group 1 were found, but no BCCs in mice from group 2. The difference was statistically significant (P = 0.001).


CONCLUSIONS
Weekly suberythematous PDT sessions with topical MAL were able to delay the development of microscopic BCCs in PTCH mice chronically exposed to UV radiation.
University of Montreal Hospital Center, Dermatology, Montreal, Quebec, Canada.
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Caty
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Liu
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Viau
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Bissonnette
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000235:genetics; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects
D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D017319:Photosensitizing Agents; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid