Interactions between antitumor drugs and radiation in mammalian tumor cell lines: differential drug responses and mechanisms of resistance following fractionated X-irradiation or continuous drug exposure in vitro

Journal Article · Fri Jan 01 00:00:00 EST 1988 · NCI Monogr.; (United States)

OSTI ID:6992491

Hill, B T; Whelan, R D; Hosking, L K; Shellard, S A; Bedford, P; Lock, R B

Drug-resistant mammalian tumor cell lines have been derived by either fractionated x-irradiation treatment or exposure to vincristine or etoposide (VP-16-213) in vitro. Analyses of the patterns of responses expressed by these differently derived, resistant cell lines have shown variations in responses to a range of antitumor drugs depending upon the agent used to induce resistance. However, all treated cell lines express resistance to vincristine and, with one exception, to VP-16-213. Preliminary evidence has indicated that resistance to vincristine in drug-treated cells, but not x-irradiation-treated cells, is associated with impaired vincristine uptake; resistance to VP-16-213 in both differently derived, resistant sublines is associated with a reduction of VP-16-213-induced DNA single-strand breakage; and collateral sensitivity to cisplatin in x-irradiation-treated cells is associated with enhanced drug-induced DNA cross-linking. These data indicate that patterns of responses to antitumor drugs and the mechanisms associated with these altered responses differ depending upon the agent used to induce resistance.

• Research Organization: Imperial Cancer Research Fund, London (England)
• OSTI ID: 6992491
• Journal Information: NCI Monogr.; (United States), Vol. 6
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTINEOPLASTIC DRUGS
RADIOSENSITIVITY EFFECTS
STRAND BREAKS
RADIOINDUCTION
TUMOR CELLS
SENSITIVITY
CROSS-LINKING
DNA
FRACTIONATED IRRADIATION
MAMMALS
X RADIATION
ANIMAL CELLS
ANIMALS
CHEMICAL REACTIONS
DRUGS
ELECTROMAGNETIC RADIATION
IONIZING RADIATIONS
IRRADIATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POLYMERIZATION
RADIATIONS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture