Nalidixic acid-resistant V79 cells with reduced DNA topoisomerase II activity and amplification prone phenotype.
Spontaneously nalidixic acid-resistant lines (NAr lines) were selected from a V79 Chinese hamster cell line and phenotypically characterized. NAr lines showed an increased doubling time, a higher number of spontaneous SCE, and more interestingly, decreased DNA topoisomerase II activity. These lines were also cross-resistant to the eukaryotic topoisomerase II inhibitors etoposide and adriamycin, but showed the same level of sensitivity as the parental line to the DNA topoisomerase I inhibitor camptothecin. NAr lines were cross-resistant to other drugs, such as PALA, MTX and MPA, resistance to which has been shown to arise by amplification of the target genes. This last feature, together with enhanced cross-resistance to PALA and MTX when employed simultaneously, suggests that NAr lines have an 'amplification prone' phenotype. From these results the decreased activity of topoisomerase II seems to be involved in the generation of amplified sequences possibly by affecting recombinational events underlying gene amplification.
Di Leonardo
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Dipartimento di Biologia Cellulare e dello Sviluppo A. Monroy, University of Palermo, Italy.
Maddalena
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Cavolina
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P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology; D005784:Gene Amplification / Q000187:drug effects*; D008647:Mesocricetus; D009268:Nalidixic Acid / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012854:Sister Chromatid Exchange / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D009268:Nalidixic Acid; D005047:Etoposide; D004317:Doxorubicin; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II