|
|
Journal of the Korean Society for Therapeutic Radiology 1997;15(3): 187-196. |
| Induction of Apoptosis and Expression of Apoptosis-related Gene Products in Response to Radiation in Murine Tumors |
| Jinsil Seong, Nancy R Hunter, Luka Milas |
1Department of Radiation Oncology, Yonsei University Medical College, Seoul, Korea.
2Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston TX 77030, USA. |
|
|
|
|
|
| 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. |
| Key Words:
Apoptosis, Murine tumors, Radiation, p53, p21waf1/cip1, Bax and bcl-2 |
|
|
|
PDF Links
Full text via DOI 
Download Citation 
