Enhanced efflux of (/sup 3/H)vinblastine from Chinese hamster ovary cells transfected with a full-length complementary DNA clone for the mdr1 gene

Journal Article · Sat Jul 15 00:00:00 EDT 1989 · Cancer Res.; (United States)

OSTI ID:5604264

Hammond, J R; Johnstone, R M; Gros, P

Multidrug-resistant Chinese hamster ovary cell clones stably transfected with, and overexpressing, the mouse mdr1 complementary DNA clone along with drug-sensitive Chinese hamster ovary control cells were characterized for their capacities to accumulate and retain (/sup 3/H)vinblastine. Multidrug-resistant mdr1 transfectants show a 3-4-fold decrease in (/sup 3/H)vinblastine accumulation, compared to their drug-sensitive counterparts. After ATP depletion, this difference in (/sup 3/H)vinblastine accumulation between mdr1 transfectants and control cells effectively disappears. This ATP-dependent decreased drug accumulation is paralleled in mdr1 transfectants by an enhanced capacity of these cells to extrude the drug in an ATP-dependent manner. In medium containing glucose and glutamine, the mdr1 transfectants release preloaded drug at a rate five times that of control, drug-sensitive cells. In ATP-depleted control and mdr1-transfected cells, there is little difference in the rate or extent of (/sup 3/H)vinblastine release. The observation that the mdr1 transfectants show a decreased (/sup 3/H)vinblastine accumulation and an increased vinblastine release, both of which are abolished when cellular ATP levels are reduced, provides a direct demonstration that the product of the transfected mdr1 gene is responsible for a mechanism controlling cellular drug levels in an ATP-dependent manner. However, attempts to establish competition for (/sup 3/H)vinblastine transport by vincristine, daunomycin, and actinomycin D were only partly successful in mdr1 transfectants.

• Research Organization: McGill Univ., Montreal (Canada)
• OSTI ID: 5604264
• Journal Information: Cancer Res.; (United States), Vol. 49:14
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHO CELLS
SENSITIVITY
VINBLASTINE
MEMBRANE TRANSPORT
ATP
CLONE CELLS
DNA
GENES
HAMSTERS
PLASMIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
AROMATICS
AZAARENES
AZOLES
CELL CONSTITUENTS
CELL CULTURES
DRUGS
HETEROCYCLIC COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques