Radiation resistance in a doxorubicin-resistant human fibrosarcoma cell line.
In clinical practice, cancers refractory to chemotherapy can appear relatively radioresistant. Recent work in multidrug-resistant cell lines has yielded conflicting results concerning the relationship between drug resistance and radiation resistance. The current study examines the radiation response of a human fibrosarcoma (HT1080) and a doxorubicin-resistant subline (HT1080/DR4). Using soft-agar colony formation after graded doses of x-rays as an endpoint, HT1080/DR4 had an increased D0 (D0 = 2.1 Gy) and a broader initial shoulder (n = 2.7, Dq = 2.1 Gy) than the parental HT1080 line (D0 = 0.7, Gy, n = 1.2, Dq = 0.3 Gy), suggesting that HT1080/DR4 has an increased capacity to repair radiation-induced DNA damage. This possibility was tested by comparing the cell lines' ability to accumulate sublethal damage. In split-dose recovery experiments, HT1080/DR4 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation, compared with the HT1080 parental line. The mechanism for this radiation resistance is not clear, but a variety of cellular alterations seen in drug-resistant cell lines are discussed with reference to areas of further study.
Miller
P R
PR
Department of Radiation Oncology, University of Arizona, College of Medicine, Tucson 85724.
Hill
A B
AB
Slovak
M L
ML
Shimm
D S
DS
D002453:Cell Cycle; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005354:Fibrosarcoma / Q000473:pathology / Q000532:radiotherapy*; D005434:Flow Cytometry; D006801:Humans; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D004317:Doxorubicin