Drug resistance following irradiation of RIF-1 tumors: influence of the interval between irradiation and drug treatment. Int J Radiat Oncol Biol Phys 1990 Sep;19(3):643-50
Date
09/01/1990Pubmed ID
2211211DOI
10.1016/0360-3016(90)90491-2Scopus ID
2-s2.0-0025005714 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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.
Author List
Hopwood LE, Davies BM, Moulder JEMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Cell Line
Combined Modality Therapy
Dose-Response Relationship, Radiation
Doxorubicin
Drug Resistance
Fluorouracil
Methotrexate
Mice
Neoplasm Transplantation
Neoplasms, Experimental
Time Factors