p53 status, cellular recovery and cell cycle arrest as prognosticators of in vitro radiosensitivity in human pancreatic adenocarcinoma cell lines

Purpose: To investigate the factors contributing to the in vitro radiosensi tivity of four human pancreatic adenocarcinoma cell lines differing in p53 status, and the basis for the lack of postirradiation G(1) arrest in the tw o cell lines that have retained a wild-type p53 allele. Materials and methods: Cells were X-irradiated and the parameters related t o radiosensitivity, as well as the modulation of gene products linked to re gulation of cell cycle transit (p53, p21/WAF1/CIP1, pRb) or DNA replication and repair (DNA topoisomerase I and II), were determined. Results: Both cell lines expressing either mutant (mt) R248W or R273H p53 p roteins were more radioresistant. All the cell lines arrested in G(1). None of the cell lines arrested in G(1) and this was linked to the inability to upregulate p21/WAF1/CIP1. There were no correlations between p53 status an d the magnitude or time of maximum G(2) arrest. However, there was a negati ve correlation between a protracted arrest in G(2) and the ability to recov er from potentially lethal damage (PLD). Conclusions: Variation in radiosensitivity is related to p53 status, but th e survival advantage conferred by having mutant p53 status is not readily e xplained neither by recovery from PLD nor by cell cycle arrest kinetics. Th ere is no p53-independent pathway for the recruitment of p21 in these cell lines following irradiation.