High levels of p53 protein in UV-irradiated normal human skin.

Exposure of normal adult human skin to doses of UV irradiation that induced mild sunburn resulted in the rapid appearance of p53 protein in the epidermis and superficial dermal fibroblasts. Immunohistological analysis with a panel of antibodies established that while p53 staining was not seen in normal skin it appeared within 2 h of UV exposure. The level of p53 immunostaining peaked at 24 h and returned to undetectable levels within 360 h. The induction of proliferating cell nuclear antigen (PCNA) (which is required for both DNA replication and repair) followed a similar spatial and temporal pattern to p53. The UV irradiation did not induce a mitotic response or the replication-associated antigens DNA polymerase alpha or Ki67. The accumulation of high levels of p53 and PCNA in response to UV doses to which many human populations are routinely exposed provides strong support for a model in which normal p53 acts as part of the DNA damage response in vertebrate cells. Such a model is consistent with the profound tumour-suppressor function of the p53 gene, the high rate of p53 mutation in neoplasia and the exceptionally high tumour susceptibility of p53-deficient mice.

The action spectrum for induction of chronic actinic dermatitis is similar to that for sunburn inflammation.

The action spectrum for induction of the abnormal cutaneous response at 24 h in the photosensitivity disorder chronic actinic dermatitis (CAD) was determined in 15 patients and found to be the same in shape as that for normal sunburn in fair-skinned individuals at 24 h, as determined for 47 control volunteers, although displaced in magnitude. This suggests that an endogenous chromophore(s), the same as or similar to that/those responsible for human sunburn, may be responsible for initiation of the abnormal reaction to irradiation in CAD, and that the putative antigen associated with the CAD reaction may be derived from that/those or associated molecules.

The efficacy of psoralen photochemotherapy in the treatment of aquagenic pruritus.

Psoralen photochemotherapy (PUVA) was effective in the treatment of five patients with aquagenic pruritus, associated in one with polycythaemia rubra vera and in another with the myelodysplastic syndrome. Relapse occurred within 2-24 weeks when treatment was discontinued. Maintenance therapy or a further course of PUVA was necessary to maintain remission. This requirement may limit the value of the therapy.