The expression of p21/WAF-1 and cyclin B1 mediate mitotic delay in x-irradiated fibroblasts.

BACKGROUND To better understand the relationship between mitotic delay and the disruption of cyclin B1 and p21 in x-irradiated fibroblasts, studies were carried out to establish correlations between the downregulation of cyclin B1 by the cyclin kinase inhibitor (CKI) p21 and the induction of mitotic delay in the NIH3T3 fibroblast. MATERIALS AND METHODS Cell cycle kinetics were used to analyze mitotic delay in irradiated NIH3T3 cells and immunocytochemistry incorporated to assess the expression of cyclin B1 and p21, following 2 or 4 Gy x-irradiation. RESULTS AND DISCUSSION Results indicate a dose dependent increase in mitotic delay accompanied by a downregulation of cyclin B1 and corresponding upregulation of the CKI p21 in exponentially growing cultures. Data indicates that the induction of radiation-induced division delay appears to be dependent on the p21 inhibition of cyclin B1 and, furthermore, p21 and cyclin B1 expression are highly dependent on cell density.