Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a > 25,000-fold collateral resistance to meth...

Ovarian cancer is the leading cause of death among gynaecological malignancies. Multiple drug resistance makes cancer cells insensitive to chemotherapy. In this study, we developed six primary ovarian cancer cell lines (W1MR, W1CR, W1DR, W1VR, W1TR, and W1PR) resistant to drugs such as methotrexate, cisplatin, doxorubicin, vincristine, topotecan, and paclitaxel. A chemosensitivity assay MTT tes...

The effectiveness of many clinically useful anticancer drugs can be severely limited by drug resistance, which appears to be intrinsic to some tumors but can also arise during multiple courses of chemotherapy in the case of many others. Studies carried out using cultured tumor cell models and other systems have established that a variety of mechanisms can contribute to drug resistance (1-3). Th...

Simultaneous use of nonsteroidal anti-inflammatory drugs (NSAIDs), probenecid, and other drugs has been reported to delay the plasma elimination of methotrexate in patients. Previously, we have reported that inhibition of the uptake process cannot explain such drug-drug interactions using rats. The present study quantitatively evaluated the possible role of the transporters in such drug-drug in...

methotrexate is an antineopalstic agent widely used in low dose to treat patients with rheumatoid arthritis. it is known to induce micronuclei at multiple doses in rats. the present study investigates the effect of vitamin a on methotrexate-induced micronuclei in rat bone marrow erythrocytes. male wistar rats were (n=5) injected with 0, 8, 16 and20mg/kg methotrexate (single i.p dose). a group o...

Ubiquitin-dependent proteolysis is a major proteolytic pathway in the cytoplasm and nucleus of eukaryotic cells. We introduced a gene encoding a substrate for this pathway into the genome of Arabidopsis thaliana. The transgene codes for a hybrid protein consisting of dihydrofolate reductase (DHFR, EC 1.5.1.3) fused to a degradation signal that is specifically recognized by components of the ubi...

The relative resistance of liver cells in primary monolayer cell culture to the cytocidal effects of methotrexate, Adriamycin, cycloheximide, or aflatoxin Bi was studied using cells derived from normal rats, rats subjected to two-thirds hepatectomy, or rats fed dietary carcinogen. Normal rat liver cells were highly sensitive to the toxic effects of methotrexate, Adriamycin, cycloheximide, and a...

Mismatch repair (MMR)-deficient cells are shown to produce >15-fold more methotrexate-resistant colonies than MMR normal cells. The increased resistance to methotrexate is primarily due to gene amplification since all the resistant clones contain double-minute chromosomes and increased copy numbers of the DHFR gene. In addition, integration of linearized or retroviral DNAs into chromosomes is a...