ATX-S10(Na)-photodynamic therapy is less carcinogenic for mouse skin compared with ultraviolet B irradiation.
BACKGROUND
Photodynamic therapy (PDT) is available for the treatment of various skin tumours and other skin diseases. Ultraviolet (UV) irradiation induces DNA damage, cyclobutane pyrimidine dimers (CPD) (6-4) photoproducts (6-4PP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), all of which are carcinogenic for the skin. However, effects of PDT on DNA damage and carcinogenesis are unclear.


OBJECTIVE
To compare the production of photoproducts and the induction of skin tumours in mouse epidermis treated with UVB or PDT.


METHODS
We performed UVB irradiation or ATX-S10(Na)-PDT on the skin of 20 hairless mice, in each case, and analysed DNA damage and tumour induction.


RESULTS
After a single irradiation of UVB on mouse skin, CPD, 6-4PP and 8-OHdG were detected in the nuclei of keratinocytes. In contrast, PDT-treated mouse keratinocytes showed induction of 8-OHdG, but not of CPD or 6-4PP. Skin tumours induced by UVB irradiation (3 kJ m(-2) three times weekly) were observed following 15 weeks of irradiation (mean +/- SEM tumour incidence 3.2 +/- 1.8%; tumour number 3.2 +/- 1.6 per mouse) and increased depending on irradiation times and doses. Following 30 weeks of UVB irradiation (3 kJ m(-2) three times weekly), mean +/- SEM tumour incidence and tumour number were 28.7 +/- 4.8% and 14.2 +/- 2.8% per mouse, respectively. Although skin tumours were also detected in PDT-treated mouse skin following 80 weeks of treatment (mean +/- SEM tumour incidence 9.1 +/- 1.8%; tumour number 12.2 +/- 2.3 per mouse), the number of tumours was not statistically different from untreated mouse skin (mean +/- SEM tumour incidence 4.1 +/- 3.8%; tumour number 5.2 +/- 3.3 per mouse).


CONCLUSIONS
PDT induced 8-OHDG but not CPD or 6-4PP, and was shown to be a relatively safe modality following multiple applications to mouse skin.
Takahashi
H
H
Department of Dermatology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan.
Nakajima
S
S
Sakata
I
I
Ishida-Yamamoto
A
A
Iizuka
H
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000378:metabolism; D010778:Photochemotherapy / Q000009:adverse effects*; D011166:Porphyrins / Q000633:toxicity*; D011740:Pyrimidine Dimers / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D014467:Ultraviolet Therapy / Q000009:adverse effects*
C115550:ATX-S10; D011166:Porphyrins; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine