Sensitization processes in human tumor cells during protracted irradiation: possible exploitation in the clinic

Jerry R. Williams, Yong Gang Zhang, Larry E. Dillehay

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies documenting the response of several human tumor cell lines to protracted, continuous irradiation and to acutely delivered radiation, suggest that tumor control may be enhanced with a tumor therapy combining external beam fractionated therapy and protracted irradiation from radiolabeled antibodies. We have evaluated the cytotoxic effect of continuous, protracted irradiation (0.005 Gy/hr to 0.50 Gy/hr) and acutely delivered high-dose-rate irradiation (1.0 Gy/min) on monolayer cultures of human tumor cell lines. Colony formation in these studies was analyzed by the seven-parameter simulation model of Dillehay. Additionally, for some cell lines, cultures were challenged during irradiation with an acute dose of 2.5, 5.0, 7.5 or 10.0 Gy at high-dose-rate. Results from these various studies indicate an altered cellular radiosensitivity occurs for some cell lines during protracted irradiation. At least two mechanisms have been identified that underlie this altered radiosensitivity. One mechanism, G2B, associated with redistribution within the cell cycle, has been previously described by Mitchell and others, and is associated with the phenomenon termed "the inverse dose-rate effect". The other mechanism is only observable following a challenge by acute high-dose-rate irradiation. We have termed this phenomenon "protracted-exposure-sensitization." The characteristics of these two mechanisms are discussed from the perspective of clinical therapeutic exploitation of combined external beam fractionated therapy and radiolabeled immunoglobulin therapy.

Original languageEnglish (US)
Pages (from-to)699-704
Number of pages6
JournalInternational journal of radiation oncology, biology, physics
Volume24
Issue number4
DOIs
StatePublished - 1992

Keywords

  • Cellular radiosensitivity
  • Combined tumor therapy
  • Dose rate effects
  • Models

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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