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- W2022252131 abstract "Abstract Mouse leukemia L1210 cells were treated with increasing concentrations of drugs that targeted the specific subunits of ribonucleotide reductase. From these studies mutant L1210 cell lines were selected that showed resistance to hydroxyurea (HU-R), deoxyadenosine (Y-8), MAIQ (MQ-580) and IMPY/deoxyadenosine (ED2). These cell lines had specific alterations that related directly to the ribonucleotide reductase site. These molecular changes included gene amplification, increased mRNA, increased enzyme activity and loss of sensitivity to dATP as a negative effector. However, each of the resistant cell lines did not have all of these changes. In addition to these changes, targeted at the ribonucleotide reductase site, the MQ-580, Y-8 and ED2 drug resistant cell lines had other alterations that are not readily attributable to the ribonucleotide reductase site. These changes included induced expression of MDR1, MRP (MQ-580), increased c-myc and c-fos expression (Y-8 and ED2), decreased p53 levels (Y-8 and ED2), increased frequency of CAD amplification (Y-8 and ED2), increased sensitivity to X-irradiation (Y-8) and a p53-independent pathway for apoptosis (Y-8). These data show that the development of drug resistance is complicated by the evolution of multifactorial mechanisms that may not be overtly related to the mechanism of action of the drug used to induce the resistance phenotype." @default.
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- W2022252131 title "Multifactorial mechanisms of drug resistance in tumor cell populations selected for resistance to specific chemotherapeutic agents" @default.
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- W2022252131 doi "https://doi.org/10.1016/s0065-2571(97)00003-4" @default.
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