[kemoo]

A clone of cancer cells is resistant to vincristine, doxorubicin, and dactinomycin but not to methotrexate and various alkylating agents. The mechanism of resistance is most likely to involve

A ) Absence of superoxide dismutase

B ) Altered DNA polymerase

C ) Enhanced drug transport out of the cell

D ) Inability to form polyglutamates

E ) Increased DNase

 

[khanar]

I'd choose C.
Vincristine and doxorubicin and dactinomycin work on the mitotic spindle formation.

Am not sure though :notsure:

 

[aktorque]

Correct answer is C) Enhanced drug transport out of the cell

Multidrug resistance to chemotherapeutic drugs such as (vincristine, doxorubicin, dactinomycin) occurs due to stepwise selection and amplification of gene that codes for a transmembrane protein (P-glycoprotein)... this transmembrane P-protein is ATP-dependent pump, which has six membrane-spanning loops forming a central channel for pumping of drugs from the cell....

Note: P-glycoprotein is normally expressed at low levels in most cell types...

Hope this help you...

 

[aktorque]

Resistance to methotrexate can be due to:

Resistance to methotrexate can be due to:

a) amplification (production of additional copies) of the gene that codes for dihydrofolate reductase resulting in increased levels of this enzyme.

b) diminishing dihydrofolate reductase affinity for MTX.

c) reduced influx of MTX, caused by a change in the carrier-mediated transport responsible for pumping methotrexate into the cell...

 

[docord]

Answer: C

Explanations

Resistance to Cytotoxic Drugs
A major problem in cancer chemotherapy is drug resistance. Some tumor types, eg, malignant melanoma, renal cell cancer, and brain cancer, exhibit primary resistance, ie, absence of response on the first exposure, to currently available standard agents. The presence of inherent drug resistance is felt to be tightly associated with the genomic instability associated with the development of most cancers. Acquired resistance develops in a number of drug-sensitive tumor types. Experimentally, drug resistance can be highly specific to a single drug and usually is based on a change in the genetic apparatus of a given tumor cell with amplification or increased expression of one or more specific genes. In other instances, a multidrug-resistant phenotype occurs resistance to a variety of natural product anticancer drugs of differing structures developing after exposure to a single agent. This form of multidrug resistance is often associated with increased expression of a normal gene (the MDR1 gene) for a cell surface glycoprotein (Pglycoprotein) involved in drug efflux. This transport molecule requires ATP to expel a variety of foreign molecules (not limited to antitumor drugs) from the cell. It is expressed constitutively in normal tissues such as the epithelial cells of the kidney, large intestine, and adrenal gland as well as in a variety of tumors. Multidrug resistance can be reversed experimentally by calcium channel blockers, such as verapamil, and a variety of other drugs, which inhibit the transporter. Other mechanisms of multiple drug resistance involve overexpression of the multidrug resistance protein 1 (MRP1), a member of the ATP-binding cassette transmembrane transporter superfamily that now consists of nine members (MRP1-MRP9). MRP1, the most extensively studied, increases resistance to natural product drugs such as anthracyclines, vinca alkaloids, taxanes, and epipodophyllotoxins by functioning as a drug export pump.

*this document is a copy&paste from here:
http://www.aippg.net/forum/f18/clone-cancer-cells-resistant-83216/