Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the genetic and biochemical bases for drug resistance and the order of appearance of different mechanisms underlying the increasingly more resistant murine erythroleukemia cell lines established in Adriamycin (ADR). In the first-step low-level resistant cell line PC4-A5 (able to grow in 5 ng/mL ADR), there was a 2-fold reduction in topoisomerase IIalpha and topoisomerase IIbeta mRNA levels, as well as topoisomerase IIalpha protein and activity levels as compared with the parental cell line. The topoisomerase IIalpha activity levels remained reduced as the cells became increasingly more resistant. In contrast, the topoisomerase II mRNA and protein levels returned to approximately the parental levels in resistant cells growing in higher drug concentrations (40-160 ng/mL). Parental cells expressed the multidrug resistance protein (MRP), but beginning with PC4-A5 MRP expression decreased and remained reduced in increasingly resistant cell lines. At high levels of ADR resistance, the cells expressed the mdr3 gene concomitant with the appearance of vincristine resistance and energy-dependent daunomycin and vincristine efflux. Glutathione levels, internal pH, and expression of the major vault protein (MVP) remained unchanged in all cell lines. Fluorescence microscopy revealed no alterations in daunomycin distribution or vesicle numbers between the parental and resistant cell lines. Different resistance mechanisms emerge sequentially as cells become more resistant to ADR; the mechanisms are retained during the development of multidrug resistance (MDR). In intermediate-level MDR cell lines (PC4-A10 and PC4-A20), resistance involves an as yet undetermined mechanism(s).
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PMID:Emergence of different mechanisms of resistance in the evolution of multidrug resistance in murine erythroleukemia cell lines. 939 72

Marine organisms and especially those living in tidal zones are confronted with dramatic changes in their environment such as temperature fluctuations on a daily and/or seasonal basis. In the present study, we investigated whether these parameters affect expression of multixenobiotic resistance (MXR)-related genes that serve as a first line of defense against a broad spectrum of natural and man-made toxicants. Expression of MXR-related genes seems to be an appropriate biomarker to determine hazardous effects of chemicals in contaminated marine habitats. The interference of natural environmental factors in the expression of biomarkers is an important issue with respect to the use of biomarkers in monitoring biological effects of pollutants, making interpretations difficult. We studied the effects of temperature, salinity and oxygen supply (anaerobiosis) on expression of MXR-related genes in gills and digestive gland of the blue mussel Mytilus edulis in order to differentiate between pollution-induced stress and responses to natural environmental variations. We found changes in expression levels of P-glycoprotein (pgp), major vault protein (mvp), topoisomerase II (topoII), heat shock protein 70 (hsp70), but not of the multidrug resistance-related protein (mrp2) genes, in laboratory experiments in relation to high temperature, low salinity and anaerobiosis but not low temperature. These effects of environmental factors have to be considered in sampling strategies for monitoring programmes to prevent false interpretation of results.
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PMID:Regulation of expression of multixenobiotic resistance (MXR) genes by environmental factors in the blue mussel Mytilus edulis. 1521 Feb 93