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KMID : 0362919970150030187
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Journal of the Korean Society for Therapeutic Radiology and Oncology
1997 Volume.15 No. 3 p.187 ~ p.196
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Induction of Apoptosis and Expression ofApoptosis-related Gene Products in Responseto Radiation in Murine Tumors
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Seong Jin-Sil
Nancy R. Hunter
Luka Milas
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Abstract
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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.
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KEYWORD
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Apoptosis, Murine tumors, Radiation, p53, p21waf1/cip1, Bax and bcl-2
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