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Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

Authors
Journal
International Journal of Radiation Oncology*Biology*Physics
0360-3016
Publisher
Elsevier
Publication Date
Volume
20
Issue
2
Identifiers
DOI: 10.1016/0360-3016(91)90092-i
Keywords
  • Session I: Effectiveness Of Combined Treatment: Laboratory Studies
Disciplines
  • Ecology
  • Geography

Abstract

Abstract The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etopside (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual. We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.

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