Effect of retinoic acid on the radiosensitivity of normal human oral keratinocyte.
- Author:
Jean LEE
1
;
Min Suk HEO
;
Sam Sun LEE
;
Sung Ook OH
;
Sul Mi LEE
;
Hang Moon CHOI
;
Soon Chul CHOI
;
Tae Won PARK
Author Information
1. Department of Oral and Maxillofacial Radiology and Dental Research Institute, College of Dentistry, Seoul National University, Korea. raylee@snu.ac.kr
- Publication Type:Original Article
- Keywords:
kerainocyte;
radiation;
ionizing;
retinoids
- MeSH:
Apoptosis;
Blotting, Western;
Cell Cycle Checkpoints;
Cell Survival;
Flow Cytometry;
Humans*;
Keratinocytes*;
Mitosis;
Necrosis;
Radiation Tolerance*;
Radiation-Sensitizing Agents;
Retinoids;
Tretinoin*
- From:Korean Journal of Oral and Maxillofacial Radiology
2003;33(2):97-105
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: To evaluate the effect of all-trans-retinoic acid (ATRA) on the radiosensitivity of normal human oral keratinocyte (NHOK). MATERIALS AND METHODS: 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 alpha and beta 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. RESULTS: Treatment with ATRA resulted in a significant decrease of SF2 value for NHOK from 0.63 to 0.27, and increased alpha and beta 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 casued 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. CONCLUSION: These results suggested that ATRA increase radiosensitivity by inhibiting mitosis caused by increasing G2 arrest.
