Characteristics of the karyotype changes in Djungarian hamster cells resistant to methotrexate

The chromosomes stained by trypsin G-banding technique were studied in five Djungarian hamster cell sublines, resistant to different concentrations of methotrexate. In all cells of two independent sublines, approximately 13 times more resistant to the drug, an additional material on the distal part of the short arm of chromosome 3 was revealed. The size and banding pattern of this new material were different in two sublines and in individual cells of each subline. In cells, which were 25-fold resistant to methotrexate, the additional material was found both in the short arm of chromosome 3 and in the long arm of chromosome 4. In some cells the additional material in chromosome 4 contained the long homogeneously staining regions (HSRs). In a subline which was 100-fold resistant to methotrexate, all cells had the chromosome 4 bearing the long HSR. The further increase in the level of drug resistance (300-fold) was accompanied by the increase in the size of HSRs in chromosome 4, the appearance of the second HSR in the short arm of chromosome 3 and emergence of small chromatin bodies. In cells with trisomy 4 and a low level of colchicine-resistance, methotrexate-resistance arises more frequently than in colchicine-sensitive cells bearing two chromosomes 4, or in cells possessing the high level of colchicine-resistance and trisomy of the short arm of chromosome 4 only. The similarities and differences of karyotypic alterations accompanying the development of colchicine- and methotrexate-resistance in Djungarian hamster cells, are discussed.