Unscheduled DNA synthesis in psoriatic skin after ultraviolet irradiation and the effects of a combined treatment with 8-methoxypsoralen and longwave ultraviolet radiation: a clinical study*

Abstract

Biopsies were taken from psoriatic patients undergoing photochemotherapy and then studied by autoradiography to investigate possible unscheduled DNA synthesis (UDS) following 8-MOP photodamage in epidermal cels. No sparse labelling was found in seventy samples taken from twenty-four different patients during PUVA therapy, indicating a lack of UDS. In contrast, UDS was observed in three patients irradiated with an all-spectrum UV lamp, as a test for DNA damage and excision repair activity. The incorporation of 3HTdR in these keratinocytes which were not undergoing S-phase was not affected by the dose of UV-A received during different stages of PUVA treatment. The results are discussed in terms of repair of the induced photodamage at the level of DNA, and in relation to a possible risk of this treatment when it is given over a long period of time.

Induction of unscheduled DNA synthesis in hairless mouse epidermis by 8-methoxypsoralen plus ultraviolet A(PUVA).

“…Thus, the induction of UDS by PUVA was far smaller than that by 4-nitroquinoline 1-oxide (4NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or UV-B irradiation (Mori et al, 1999(Mori et al, , 2000a. In studies in vivo or in vivo -in vitro by an autoradiographic method, previous investigators have failed to detect induction of UDS (Epstein and Fukuyama, 1975;Bioulac et al, 1980;Hönigsmann et al, 1981;Bishop and Abel, 1985). Our success in the detection of UDS induction in vivo -in vitro in the present study might have been due to the carefully designed experimental procedures that we employed.…”

“…For example, we used a UV-absorbing glass filter in order to eliminate the wavelength range of UV-B. In other studies, a UV-absorbing glass filter was not used (Bioulac et al, 1980), or a plate glass with a low UV-absorbing effect was used (Bishop and Abel, 1985). The presence of UV-B would increase the control level of DNA synthesis, and thereby mask slight induction of UDS by PUVA.…”

“…Hönigsmann et al (1981) failed to detect induction of UDS by PUVA in healthy human epidermis in vivo -in vitro by autoradiography. Bioulac et al (1980), and Bishop and Abel (1985) also found no induction of UDS by PUVA in skin from psoriatic patients in vivo -in vitro by autoradiography. We recently reported induction of UDS by skin carcinogens (Mori et al, 1999) and UV irradiation (Mori et al, 2000a), and we also evaluated age-related changes of DNA repair capacity in the epidermis of hairless mice by assaying induction of UDS after UV-B irradiation (Mori et al, 2000b), using a modification of the in vivo -in vitro liquid scintillation counting methods which had been developed for UDS studies in the glandular stomach, forestomach, colon and liver of rats (Furihata et al, 1984(Furihata et al, , 1985Furihata and Matsushima, 1987;Sawada et al, 1989;Ohsawa et al, 1993;Furihata and Matsushima, 1995).…”

Autoradiographic Study of the Effects of Psoralen and Ultraviolet Light on DNA, RNA and Protein Synthesis in Cultured Keratinocytes and Psoriatic Skin

“…In vivo in man, the mechanism of the antipro liferative action of PUVA therapy in the remission of psoriasis is not yet clear, al though in vitro studies have shown that the major cytotoxic effect due to psoralens and UVA light occurs via the inhibition of semi conservative DNA synthesis. In fact, despite the numerous in vivo reports on animals [14,34,35] and also in psoriatic patients [12,13], DNA synthesis inhibition as well as DNA repair synthesis [36][37][38][39] have not been un equivocally demonstrated.…”

Psoralens, Uva (Puva) and Photocarcinogenesis

“…Comparing angelicin to 8-MOP, it was found that much higher concentrations of angelicin were necessary to photo-suppress DNA synthesis [30,40]. Unscheduled DNA synthesis, which appears to represent DNA damage and excision repair activity, was lacking in skin samples taken from patients during PUVA therapy [4]. This was compared to the skin of patients irradiated with an all-spectrum UV light in whom unscheduled DNA synthesis was observed.…”