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.
ASJC Scopus subject areas