Radiation-induced concomitant overexpression of p53, p62c-fos and p21N-fas in mouse epidermis

Abstract. Early molecular events in radiation carcinogenesis in vivo are difficult to study, especially because it is usually impossible to know in advance the exact location of a radiation-induced tumour. In the present study, we have attempted to overcome this difficulty by exposing a very small area of hairless mouse skin to high-dose beta radiation (i.e. immobilized hot particles) on the reasonable assumption that a malignant tumour would subsequently develop and be found at the exposed site in a long-term follow-up. The results showed that at an exposed site, before the appearance of a visible or histologically detectable tumour, overexpression of the product of the tumour suppressor gene p53 was common (28% of the sites studied; tested with PAbl801, PAb421, PAb240 and a polyclonal antibody CM1) and that this change was regularly accompanied by overexpression of p62^c-fos and p21^N-ras. Expression of several other oncoproteins studied (p39^c-jun, p21^K-ras, p21^H-ras) was not altered at these sites. A similar pattern of changes was observed in a visible and histopathologically distinct tumour that was analyzed after its development at an exposed site. These results suggest a re'markably regular pattern of molecular changes, induced by ionizing radiation in mouse epidermis, which might be associated with carcinogenesis.