Role of p53 in Growth Suppression by Bromodeoxyuridine in Human Gastric Cancer Cell Lines

概要

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Bromodeoxyuridine (BrdU) is known to cause base mispairs and DNA strand breaks during DNA synthesis, culminating in growth suppression. To know whether P53 gene plays any role in the BrdU-induced growth suppression, we continuously gave BrdU (20 μM) to the synchronized culture of human gastric cancer cell lines, MKN-45 (P53-wild type) and MKN-28 (P53-mutant), shortly after release from the G1/S block by hydroxyurea. In comparison with the control culture, the growth of MKN-28 was not suppressed until 48 hr of BrdU exposure, while that of MKN-45 was already suppressed at the 24 hr point. Continuous 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 comparison with synchronized control cultures of matched cell cycle phase. BrdU-exposed MKN-45 cells showed a significantly higher incidence of apoptosis after the cells passed through the first G2 phase and the second S/G2 phases, but MKN-28 did not. It thus appears that the delays of S/G2 phases and an increased incidence of apoptosis in the first cell cycle are p53-dependent. The growth suppression in the second S/G2 phase or later observed in both of the cell lines may be p53-independent.
日本組織細胞化学会の論文