Induction of Apoptosis and Expression of Apoptosis-related Gene Products in Response to Radiation in Murine Tumors.
- Author:
Jinsil SEONG
1
;
Nancy R HUNTER
;
Luka MILAS
Author Information
1. Department of Radiation Oncology, Yonsei University Medical College, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Apoptosis;
Murine tumors;
Radiation;
p53;
p21waf1/cip1;
Bax and bcl-2
- MeSH:
Apoptosis*;
Blotting, Western;
Cytotoxins;
Genes, Regulator;
Oncogenes;
Up-Regulation
- From:Journal of the Korean Society for Therapeutic Radiology
1997;15(3):187-196
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: To analyze the involvement of apoptosis regulatory genes p53, p21waf1/cip1, bax and bcl-2 in induction of apoptosis by radiation in murine tumors. MATERIALS AND METHODS: The radiation-sensitive ovarian carcinoma OCa-I, and the radiation-resistant hepatocarcinoma HCa-I were used. Tumors, 8 mm in diameter, were irradiated with 25 Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. RESULTS: Both tumors were positive for wild-type p53. Radiation induced apoptosis in OCa-I but not in HCa-I. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h. In OCa-I radiation upregulated the expression of p53, p21waf1/cip1, and the bcl-2/bax ratio was decreased. In HCa-I radiation increased the expression of both p53 and p21waf1/cip1, although the increase of the latter was small. The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis. CONCLUSIONS: The development of apoptosis required upregulation of both p53 and p21waf1/cip1 as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio prevented apoptosis in the presence of upregulated p53 and p21waf1/cip1. These findings indentified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for predicting the outcome of cancer therapy with cytotoxic agents.
