| Literature DB >> 2906349 |
K Kohno1, J Kikuchi, S Sato, H Takano, Y Saburi, K Asoh, M Kuwano.
Abstract
A multidrug-resistant clone of human cancer KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, VJ-300, obtained after ethylmethane sulfonate mutagenesis showed 400-fold higher resistance to vincristine than did KB cells. Cellular accumulation of vincristine in VJ-300 was decreased to less than one-tenth of that in KB. The cells were also cross-resistant to daunomycin, adriamycin, actinomycin D, colchicine and VP-16. During continuous culturing in the absence of any drug for several months, a different colchicine-resistant and multidrug-resistant clone, KB-C1, reverted almost completely to drug sensitivity, whereas drug resistance in VJ-300 was stably maintained. Amplification of the multidrug-resistance-1 (mdr-1) gene was more than 20-fold in KB-C1, but less than 2-fold in VJ-300. mdr-1 mRNA was, however, expressed in VJ-300 at a rate comparable to KB-C1. Acquisition of high multidrug resistance in VJ-300 might be correlated with both activated transcription of mdr-1 gene and amplification.Entities:
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Year: 1988 PMID: 2906349 PMCID: PMC5917651 DOI: 10.1111/j.1349-7006.1988.tb01550.x
Source DB: PubMed Journal: Jpn J Cancer Res ISSN: 0910-5050