Protective effects of sunscreening agents on photocarcinogenesis, photoaging, and DNA damage in XPA gene knockout mice

We investigated the protective effects of commercial sunscreening agents ag ainst UVB-induced photoresponses in group A xeroderma pigmentosum (XPA) mod el mice. XPA gene-deficient mice are defective in nucleotide excision repai r and show a high incidence of skin tumors and severe acute inflammation in response to UVB irradiation, in a similar manner to XP patients. SPF 10 an d SPF 60 sunscreens protected partially and almost completely, respectively , ear swelling responses produced by UVB up to 200 mJ/cm(2) in (-/-) mice. XPA (-/-) mice were irradiated three times a week to a cumulative dose of 2 .6 J/cm(2) UVB for a period of 24 weeks with or without SPF 10 or SPF 60 su nscreen. UV-induced skin tumors had developed in all unprotected (-/-) mice (13.3 tumors per mouse) at the completion of UVB irradiation. The SPF 60 s unscreen afforded stronger protection against photocarcinogenesis (1.0 tumo rs per mouse) than the SPF 10 sunscreen (4.4 tumors per mouse). Regarding p hotoaging, SPF 60 sunscreen also protected against mast cell infiltration ( 79% inhibition), elastic fiber accumulation, and dermal cyst proliferation in XPA (-/-) mice compared with unprotected (-/-) mice. In (-/-) mice, the SPF 60 sunscreen provided stronger protection against cyclobutane pyrimidin e dimer formation shown immunohistologically following irradiation with 200 mJ/cm(2) UVB than the SPF 10 sunscreen. The XPA model mouse is a useful an imal for the evaluation of the photoprotective ability of sunscreens becaus e photoresponses, even chronic changes, can be easily and quickly induced e xperimentally.