Retinoic acid가 사람 정상 구강각화세포의 방사선감수성에 미치는 영향에 관한 연구
Effect of retinoic acid on the radiosensitivity of normal human oral keratinocyte
이진, 허민석, 이삼선, 오성욱, 이설미, 최항문, 최순철, 박태원,
소속 상세정보
이진 ( Lee Jean ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소
허민석 ( Heo Min-Suk ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소
이삼선 ( Lee Sam-Sun ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소 및 BK21
오성욱 ( Oh Sung-Wook ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소
이설미 ( Lee Sul-Mi ) - 강릉대학교 치과대학 구강악안면방사선학교실
최항문 ( Choi Hang-Moon ) - 강릉대학교 치과대학 구강악안면방사선학교실
최순철 ( Choi Soon-Chul ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소 및 BK21
박태원 ( Park Tae-Won ) - 서울대학교 치과대학 구강악안면방사선학교실 및 치학연구소
KMID : 0896020030330020097
Abstract
To evaluate the effect of all-trans-retinotic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). Relative cell survival fraction including SF2 (survival fraction at 2 Gy) was calculated on the basis of colony formation assay. Data were fitted to the linear-quadratic model to establish the survival curve and calculate α and β values. Using flow cytometry at 1, 2, 3, 4, and 5 days after exposure to 2 and 10 Gy irradiation, cell cycle arrest and apoptosis were analysed. To understand the molecular mechanism of the radiosensitization of ATRA on NHOK, proteins related with apoptosis and cell cycle arrest were investigated by Western blot analysis. Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased α and β value, indicating that ATRA increased radiosensitivity of NHOK. ATRA increased LDH significantly, but increasing irradiation dose decreased LDH, suggesting that the radiosensitizing effect of ATRA is not directly related with increasing cell necrosis by ATRA. ATRA did not induce appotosis but increased G2 arrest after 10 Gy irradiation, implying that the increased radiosensitivity of NHOK may be due to a decrease in mitosis caused by increasing G2 arrest. ATRA inhibited the reduction of p53 at 3 days after 10 Gy irradiation and increased p21 at 1 day after 10 Gy irradiation. Further study is required to determine the precise relationship between this effect and the radiosensitizing effect of ATRA. These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.
키워드
kerainocyte; radiation; ionizing; retinoids
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