INDUCTION OF UNSCHEDULED DNA SYNTHESIS IN HAIRLESS MOUSE EPIDERMIS BY 8-METHOXYPSORALEN PLUS ULTRAVIOLET A(PUVA)

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Induction of unscheduled DNA synthesis (UDS) by 8-methoxypsoralen (8-MOP) plus ultraviolet A(UV-A)(PUVA) was investigated in the epidermis of female hairless mice by means of an in vivo - in vitro assay using a liquid scintillation counting method. Groups of three to five 8-week-old female hairless mice had 8-MOP applied once onto two areas of the back after stripping of the stratum corneum with adhesive tape to enhance skin penetration, and were irradiated with UV-A. Skin samples were taken and cultured in a medium containing [^3H]thymidine with or without hydroxyurea (HU) for 2 hr. DNA of the epidermis was extracted, and the incorporation of [^3H]thymidine into DNA and the DNA content were determined with a liquid scintillation counter and a fluorescence spectrophotometer, respectively. Induction of UDS was judged in terms of the UDS index [(the ratio of DNA synthesis in the presence of HU to that its absence)×100]. In a time-course study, the UDS index was increased at 1, 2 and 24 hr after 1×10^5 J/m^2 UV-A irradiation with 0.001% 8-MOP, reaching the maximum level at 24 hr. In a dose-response study, it was significantly increased at the dose of 1×10^5 J/m^2 of UV-A at 24 hr with 0.001% 8-MOP, but showed no significant change at the doses of 0.5×10^5, 2×10^5 and 4×10 ^5 J/m^2. In a further study on the effect of varying the dose of 8-MOP, the UDS index was significantly increased at 0.001 and 0.002% 8-MOP at 24 hr after 1×10^5 J/m^2 UV-A irradiation, reaching the maximum level with 0.002% 8-MOP. The increase of the UDS index in these studies was less than 3-fold. These results show that PUVA causes a small induction of UDS, which might be due to slow DNA excision repair over a long period.
日本トキシコロジー学会の論文
2001-02-20

INDUCTION OF UNSCHEDULED DNA SYNTHESIS IN HAIRLESS MOUSE EPIDERMIS BY 8-METHOXYPSORALEN PLUS ULTRAVIOLET A(PUVA)

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