Alterations in the properties of mouse leukemia L1210 cell lines selected by different methods for resistance to...

Mouse leukemia L1210 cells were generated for resistance to deoxyguanosine by two different methods. In one case the L1210 cells were subjected to gradual increases in deoxyguanosine (dGuo-R); in the second approach, the cells were subjected to deoxyguanosine at a concentration ten times the IC50 value and plated out on soft agar (D-92). The dGuo-R and D-92 cell lines had different phenotypic expressions. The dGuo-R cells showed a higher degree of resistance to dGuo than the D-92 cells. The levels of resistance to other cytotoxic drugs such as araC or 2-chloro-2'-deoxyadenosine did not necessarily correlate with the degree of resistance to dGuo. Deoxycytidine kinase activity was decreased in both of the cell lines, although there was a larger decrease in the dGuo-R cell line. The levels of kinase activities toward the other substrates were not all coordinately decreased in these cell lines. The degree of resistance of these cell lines to dGuo cannot be ascribed solely to an alteration at the deoxycytidine kinase site.