Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine
Journal Article
·
· Cancer Res.; (United States)
OSTI ID:5227827
The optimum integration of chemotherapy and irradiation is of potential clinical significance in the treatment of ovarian cancer. A series of human ovarian cancer cell lines have been developed in which dose-response relationships to standard anticancer drugs have been determined, and the patterns of cross-resistance between these drugs and irradiation have been established. By stepwise incubation with drugs, sublines of A2780, a drug-sensitive cell line, have been made 100-fold, 10-fold, and 10-fold more resistant to Adriamycin (2780AD), melphalan (2780ME), and cisplatin (2780CP). Two additional cell lines, NIH:OVCAR-3nu(Ag+) and NIH:OVCAR-4(Ag+), were established from drug-refractory patients. 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) are all cross-resistant to irradiation, with DOS of 146, 187, 143, and 203, respectively. However, 2780AD remains sensitive to radiation, with a DO of 111, which is similar to that of A2780 (101). Glutathione (GSH) levels are elevated in 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) to 4.58, 6.13, 12.10, and 15.14 nmol/10(6) cells as compared to A2780, with 1.89 nmol/10(6) cells. However, the GSH level in 2780AD is only minimally higher than that in A2780 (2.94 nmol/10(6) cells). Buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly increases the radiation sensitivity of 2780ME (changing the DO from 143 to 95) and 2780CP to a lesser extent, suggesting that intracellular GSH levels may play an important role in the radiation response of certain neoplastic cells.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 5227827
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 5; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Depletion of intracellular GSH and NPSH by buthionine sulfoximine and diethyl maleate: factors that influence enhancement of aerobic radiation response
Journal Article
·
Fri Jun 15 00:00:00 EDT 2012
· Biochemical and Biophysical Research Communications
·
OSTI ID:22207893
Cellular glutathione depletion by diethyl maleate or buthionine sulfoximine: no effect of glutathione depletion on the oxygen enhancement ratio
Journal Article
·
Mon Oct 31 23:00:00 EST 1983
· Radiat. Res.; (United States)
·
OSTI ID:5011130
Depletion of intracellular GSH and NPSH by buthionine sulfoximine and diethyl maleate: factors that influence enhancement of aerobic radiation response
Conference
·
Wed Aug 01 00:00:00 EDT 1984
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
·
OSTI ID:6408307
Related Subjects
560151* -- Radiation Effects on Animals-- Man
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FEMALE GENITALS
GLUTATHIONE
GONADS
IMINES
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OVARIES
PATIENTS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATION EFFECTS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
SURVIVAL TIME
THERAPY
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
FEMALE GENITALS
GLUTATHIONE
GONADS
IMINES
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OVARIES
PATIENTS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIATION EFFECTS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
SURVIVAL TIME
THERAPY