Identification of proteins that regulate radiation-induced apoptosis in murine tumors with wild type p53

Jinsil Seong, Hae Jin Oh, Jiyoung Kim, Jeung Hee An, Wonwoo Kim

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Abstract

In this study, we investigated the molecular factors determining the induction of apoptosis by radiation. Two murine tumors syngeneic to C3H/HeJ mice were used: an ovarian carcinoma OCa-I, and a hepatocarcinoma HCa-I. Both have wild type p53, but display distinctly different radiosensitivity in terms of specific growth delay (12.7 d in OCa-I and 0.3 d in HCa-I) and tumor cure dose 50% (52.6 Gy in OCa-I and > 80 Gy in HCa-I). Eight-mm tumors on the thighs of mice were irradiated with 25 Gy and tumor samples were collected at regular time intervals after irradiation. The peak levels of apoptosis were 16.1 ± 0.6% in OCa-I and 0.2 ± 0.0% in HCa-I at 4 h after radiation, and this time point was used for subsequent proteomics analysis. Protein spots were identified by peptide mass fingerprinting with a focus on those related to apoptosis. In OCa-I tumors, radiation increased the expression of cytochrome c oxidase and Bcl2/adenovirus E1B-interacting 2 (Nip 2) protein higher than 3-fold. However in HCa-I, these two proteins showed no significant change. The results suggest that radiosensitivity in tumors with wild type p53 is regulated by a complex mechanism. Furthermore, these proteins could be molecular targets for a novel therapeutic strategy involving the regulation of radiosensitivity.

Original languageEnglish
Pages (from-to)435-441
Number of pages7
JournalJournal of radiation research
Volume48
Issue number5
DOIs
Publication statusPublished - 2007

All Science Journal Classification (ASJC) codes

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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