Induction of transcription of 'immediate early genes' by low-dose ionizing radiation

A. V. Prasad, Mohan Natarajan, B. Chandrasekar, M. L. Meltz

Research output: Contribution to journalArticle

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Abstract

The induction of transcription of specific genes after exposure to ionizing radiation has previously been reported after lethal doses of radiation (2-50 Gy). Little attention has been focused on expression of 'immediate early genes' after low doses of ionizing radiation, where cell viability remains high. This dose range (0.25-2.0 Gy) is above the diagnostic dose level but at or below the doses typical for a single exposure in fractionated radiotherapy treatment of cancer. In this study, it was observed that doses in the range of 0.25-2.0 Gy induced different amounts of the mRNAs of the proto-oncogenes c-fos, c-jun, c-myc and c-Ha-ras at a given dose and time in Epstein-Barr virus-transformed human lymphoblastoid 244B cells. A maximum response was seen after a dose of 0.5 Gy for all but c-fos, which showed a maximum response after exposure to 0.25 Gy. Time-course studies demonstrated that, for all four proto-oncogenes, the induction was transient, reaching a maximum at 1 h and declining to the constitutive level at 4 h after irradiation. Using second-messenger specific inhibitors, the signaling pathways involved in the induction of these proto-oncogenes was also investigated. The results showed that all four of the proto-oncogenes induced after 0.5 Gy shared a common pathway of tyrosine kinase activation. Other signaling pathways included protein kinase C, reactive oxygen intermediates and calcium-dependent kinases; these were found to be differentially involved in the induction of transcription of the individual proto-oncogenes. In summary, this study suggests that low-dose ionizing radiation (0.25-2.0 Gy) can modulate expression of immediate early genes. Secondly, the activation of immediate early genes after low-dose exposure involves multiple second- messenger signaling pathways. Third, the magnitude of involvement of the different signaling pathways after low-dose radiation is different for each proto-oncogene expressed.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalRadiation Research
Volume143
Issue number3
DOIs
StatePublished - 1995

Fingerprint

Immediate-Early Genes
Proto-Oncogenes
Ionizing Radiation
ionizing radiation
genes
induction
proto-oncogenes
transcription (genetics)
oncogenes
dosage
Second Messenger Systems
Radiation
fos Genes
second messengers
Human Herpesvirus 4
Protein-Tyrosine Kinases
Protein Kinase C
Cell Survival
phosphotransferases (kinases)
Phosphotransferases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Prasad, A. V., Natarajan, M., Chandrasekar, B., & Meltz, M. L. (1995). Induction of transcription of 'immediate early genes' by low-dose ionizing radiation. Radiation Research, 143(3), 263-272. https://doi.org/10.2307/3579212

Induction of transcription of 'immediate early genes' by low-dose ionizing radiation. / Prasad, A. V.; Natarajan, Mohan; Chandrasekar, B.; Meltz, M. L.

In: Radiation Research, Vol. 143, No. 3, 1995, p. 263-272.

Research output: Contribution to journalArticle

Prasad, AV, Natarajan, M, Chandrasekar, B & Meltz, ML 1995, 'Induction of transcription of 'immediate early genes' by low-dose ionizing radiation', Radiation Research, vol. 143, no. 3, pp. 263-272. https://doi.org/10.2307/3579212
Prasad, A. V. ; Natarajan, Mohan ; Chandrasekar, B. ; Meltz, M. L. / Induction of transcription of 'immediate early genes' by low-dose ionizing radiation. In: Radiation Research. 1995 ; Vol. 143, No. 3. pp. 263-272.
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