caa a22 4500 465820786 CHVBK 20180323112135.0 cr unu---uuuuu 170327e19900901xx s 000 0 eng 10.1007/BF01233191 doi (NATIONALLICENCE)springer-10.1007/BF01233191 X-ray induction of methotrexate resistance due to dhfr gene amplification [Elektronische Daten] [Peter Hahn, Barbara Nevaldine, William Morgan] The effect of ionizing radiation on methotrexate (MTX) resistance and gene amplification in cultured mammalian cells was investigated. X-irradiation of mouse EMT-6 cells induced cell killing and MTX resistance due to amplification of the dihydrofolate reductase (dhfr) gene in a dose-dependent manner. The highest yields of mutant cells were obtained at approximately D37 (the dose at which 37% of the cells survive), where the frequency of MTX-resistant cells was four- to eightfold over that of the unirradiated population. The proportion of MTX-resistant cells among the survivors increased logarithmically with dose, up to a 1000-fold increase over unirradiated cells at 1000 cGy, the highest dose tested. The induced frequency of MTX resistance after X-irradiation was greater than the induced frequency of 8-azaguanine resistance, which indicates deletion of the hypoxanthine phosphoribosyltransferase gene. Inhibition of poly(ADP-ribose) polymerase by the addition of 3-aminobenzamide before irradiation increased both cell killing and MTX resistance. Metaphase spreads of chromosomes from EMT-6 cells that had been irradiated and subjected to stepwise increases in MTX concentration showed numerous double minutes. Pulsed-field gel electrophoresis of the DNA from cells containing radiation-induced double minutes showed that many copies of the dhfr gene were present on circular DNA molecules of 106, 2× 106, and 3×106 base pairs. These results suggest a relationship between the induction of chromosome aberrations and the induction of gene amplification. Plenum Publishing Corporation, 1990 Hahn Peter Department of Radiology, State University of New York Health Science Center, 13210, Syracuse, New York aut Nevaldine Barbara Department of Radiology, State University of New York Health Science Center, 13210, Syracuse, New York aut Morgan William Laboratory of Radiobiology and Environmental Health, University of California, 94143-0750, San Francisco, California aut Somatic Cell and Molecular Genetics Kluwer Academic Publishers-Plenum Publishers 16/5(1990-09-01), 413-423 0740-7750 16:5<413 1990 16 11188 https://doi.org/10.1007/BF01233191 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01233191 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hahn Peter Department of Radiology, State University of New York Health Science Center, 13210, Syracuse, New York aut NATIONALLICENCE 700 1- Nevaldine Barbara Department of Radiology, State University of New York Health Science Center, 13210, Syracuse, New York aut NATIONALLICENCE 700 1- Morgan William Laboratory of Radiobiology and Environmental Health, University of California, 94143-0750, San Francisco, California aut NATIONALLICENCE 773 0- Somatic Cell and Molecular Genetics Kluwer Academic Publishers-Plenum Publishers 16/5(1990-09-01), 413-423 0740-7750 16:5<413 1990 16 11188 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer