Role of p53 in growth suppression by bromodeoxyuridine in human gastric cancer cell lines

Bromodeoxyuridine (BrdU) is known to cause base mispairs and DNA strand bre aks during DNA synthesis, culminating in growth suppression. To know whethe r P53 gene plays any role in the BrdU-induced growth suppression, we contin uously gave BrdU (20 muM) to the synchronized culture of human gastric canc er cell lines, MKN-45 (P53-wild type) and MKN-28 (P53-mutant). shortly afte r release from the G1/S block by hydroxyurea. In comparison with the contro l culture, the growth of MKN-28 was not suppressed until 48 hr of BrdU expo sure, while that of MKN-45 was already suppressed at the 24 hr point. Conti nuous exposure to BrdU caused a S-phase delay and G2 arrest of around 6 hr each in MKN-45 and a delay only of the second S phase In MKN-28 in comparis on with synchronized control cultures of matched cell cycle phase. BrdU-exp osed MKN-45 cells showed a significantly higher incidence of apoptosis afte r the cells passed through the first G2 phase and the second S/G2 phases, b ut MKN-28 did not. It thus appears that the delays of S/G2 phases and an in creased incidence of apoptosis in the first cell cycle are p53-dependent. T he growth suppression in the second S/G2 phase or later observed in both of the cell lines may be p53-independent.