title: Genetic status of p53 and induction of apoptosis by radiation or isoflavones in human gastric carcinoma cell lines.
abstract: We have shown previously that various human cancer cell lines undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation or isoflavones. Here, we assessed the role of p53 gene in cell cycle and apoptosis following treatment of 11 gastric carcinoma cell lines with gamma-rays, genistein, biochanin A, or daidzein. Cell survival was measured by trypan blue staining, and apoptosis was assessed by fluorochrome staining. The rate of cell survival and apoptosis of the cells by gamma-irradiation or isoflavones did not correlate with p53 gene abnormalities. Flow cytometric measurement of DNA content demonstrated that while gamma-irradiation and genistein induced G(2) arrest, biochanin A and daidzein blocked the cell cycle of all carcinoma cells at G(1) phase. At multiple time points following irradiation, G(2) arrest was observed at 12-16 h in the wild-type and mutant p53 cell lines. Induction of p53 and p21 proteins was not observed in wild-type p53 lines after exposure to gamma-irradiation or isoflavones by Western blotting. Moreover, transfection of the wild-type p53 gene into MKN-1 cells failed to induce G(1) arrest by gamma-irradiation and genistein. Based on these results, we hypothesize that gastric cancer cells may possess a signal pathway which is different from the usual mechanisms of the p53-mediated DNA damage response in normal or hematopoietic tumor cells.
authors.affiliation: HIROSHIMA UNIV,RES INST RADIAT BIOL & MED,DEPT RADIAT BIOL,MINAMI KU,HIROSHIMA 734,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,MINAMI KU,HIROSHIMA 734,JAPAN. IMMUNOBIOL LABS CO LTD,DIV MOL & CELLULAR BIOSCI,FUJIOKA 375,JAPAN.
authors.forename: K
authors.initials: K
authors.lastname: Yanagihara
authors.forename: M
authors.initials: M
authors.lastname: Numoto
authors.forename: H
authors.initials: H
authors.lastname: Tauchi
authors.forename: Y
authors.initials: Y
authors.lastname: Akama
authors.forename: H
authors.initials: H
authors.lastname: Yokozaki
authors.forename: E
authors.initials: E
authors.lastname: Tahara
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
authors.forename: T
authors.initials: T
authors.lastname: Seito