Induction of p53 expression in skin by radiotherapy and UV radiation: A randomized study

Background: p53 protein plays an important role in the response to DNA dama ge, and radiotherapy can cause radiation dermatitis, p53 and p21 levels inc rease in vitro when DNA is damaged by UVA, UVB, or gamma -radiation, To det ermine whether this response occurs in human skin and predicts the level of radiation dermatitis, we investigated levels of p53 and p21 in skin expose d to different types of radiation as part of a randomized study of women wi th breast cancer to evaluate topical steroid or emollient cream treatments for radiation dermatitis of their irradiated breast. Methods: After surgery but before receiving tangential 5-mV photo-beam radiotherapy (2 Gy and 54 Gy) to the affected breast parenchyma, multiple areas on the backs of 50 wo men were irradiated with UVA and other areas were irradiated with UVB, Skin biopsy samples were taken from areas of normal unirradiated skin and all i rradiated areas, and p53 and p21 were detected immunohistochemically, All s tatistical tests are two-sided. Results: In skin irradiated with UVA or UVB , medians of 4.4% (range = 0%-40.5%) or 45.5% (range = 5.3%-74.6%) p53-posi tive keratinocytes, respectively, were observed. Radiotherapy produced medi ans of 31.0% (range = 0%-79.3%) p53-immunoreactive cells after 2 Gy of radi ation and 83.2% (range = 37.6%-95.2%) after 54 Gy of radiation. Despite lar ge interindividual differences in p53 response, comparable increases in epi dermal p53 response were independent of the type of radiation. A correlatio n between p53 and p21 was also evident (r(s) = .78), In breast skin, there was no association between the p53 response and the degree of erythema (a m easure of radiation dermatitis) and no statistically significant difference between treatment arms and p21/p53 responses. Conclusions: Individual resp onses to radiation-induced DNA damage varied widely and may be independent of the type of radiation. The epidermal p53 response does not predict the d egree of radiation dermatitis.