The establishment of MDMS-resistant cloned cell lines from in vitro cultured, MDMS-sensitive, Yoshida sarcoma cells

A cloned cell line established from an in vivo maintained Yoshida tumour, known to be sensitive to methylene dimethanesulphonate (MDMS), was subjected to selection in vitro by repeated treatments with MDMS. After six successive clonal isolations the resultant clone showed an increase in resistance to MDMS by a factor of 10³. The cell lines selected in vitro for resistance to MDMS were not crossresistant to HN₂, suggesting that sensitivity to bifunctional alkylating agents is controlled by at least two mutations. The biphasic nature of the dose-response curves even after successive cloning indicates some instability of factors determining resistance.