skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

Abstract

RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development ofmore » tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance.« less

Authors:
; ;  [1]
  1. Medical College of Wisconsin, Milwaukee (USA)
Publication Date:
OSTI Identifier:
6321735
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics; (USA)
Additional Journal Information:
Journal Volume: 19:3; Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANTINEOPLASTIC DRUGS; RADIOSENSITIVITY EFFECTS; TUMOR CELLS; RADIOSENSITIVITY; DOSE-RESPONSE RELATIONSHIPS; EXPERIMENTAL NEOPLASMS; IN VIVO; MICE; RADIOTHERAPY; ANIMAL CELLS; ANIMALS; DRUGS; MAMMALS; MEDICINE; NUCLEAR MEDICINE; RADIOLOGY; RODENTS; THERAPY; VERTEBRATES; 550603* - Medicine- External Radiation in Therapy- (1980-); 560152 - Radiation Effects on Animals- Animals

Citation Formats

Hopwood, L E, Davies, B M, and Moulder, J E. Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment. United States: N. p., 1990. Web. doi:10.1016/0360-3016(90)90491-2.
Hopwood, L E, Davies, B M, & Moulder, J E. Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment. United States. https://doi.org/10.1016/0360-3016(90)90491-2
Hopwood, L E, Davies, B M, and Moulder, J E. 1990. "Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment". United States. https://doi.org/10.1016/0360-3016(90)90491-2.
@article{osti_6321735,
title = {Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment},
author = {Hopwood, L E and Davies, B M and Moulder, J E},
abstractNote = {RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance.},
doi = {10.1016/0360-3016(90)90491-2},
url = {https://www.osti.gov/biblio/6321735}, journal = {International Journal of Radiation Oncology, Biology and Physics; (USA)},
issn = {0360-3016},
number = ,
volume = 19:3,
place = {United States},
year = {Sat Sep 01 00:00:00 EDT 1990},
month = {Sat Sep 01 00:00:00 EDT 1990}
}