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Chromosomal Constitution and Amethopterin Resistance in Cultured Mouse Cells^*

( Departments of Experimental Therapeutics and Medicine C, Roswell Park Memorial Institute, Buffalo, New York)

The chromosomal constitutions of four amethopterin-resistant sublines of cultured Sarcoma 180 cells were compared with those of two sensitive sublines. No correlation between amethopterin resistance and chromosomes was observed. The chromosomal character of a resistant subline was completely retained in the sensitive subline derived from it after 9 months of continuous cultivation in the absence of the drug. The folic acid reductase content increased with increasing resistance and was 300–400 times higher in the 3000-fold resistant cell line than in the sensitive parent cells. Extensive selection is shown to be involved in the development of the amethopterin-resistant cell lines. This selection is most probably based on the capacity of a cell to rapidly increase the content of folic acid reductase.

^* This investigation was supported in part by research grants (CY-4175 and CS-9749) from the National Cancer Institute of the United States Public Health Service.

Received 4/ 9/62.