STUDIES ON A NEW MECHANISM OF RESISTANCE OF L5178Y MURINE LEUKEMIA CELLS TO CYTOSINE ARABINOSIDE

A mutant (car) of L5178Y murine leukemia cells has been isolated that is about 5-fold resistant to the growth inhibitory effects of cytosine arabinoside and about 25-fold resistant to the growth-inhibitory effects of deoxythymidine. The metabolism of [3H]nucleosides was compared in both the parent L5178Y cells and the car cells. There appeared to be no increased catabolism of cytosine arabinoside in the car cells and little or no difference in the incorporation of either [3H]cytosine arabinoside, [3H]deoxycytidine, or [3H]deoxythymidine into their respective mono-, di- and triphosphate forms in the two cell lines. The incorporation of [3H]cytidine and [3H]uridine into RNA and DNA of [3H]deoxythymidine into DNA of both cell lines appeared to be about the same. However, in the car cells there was an increased incorporation of [3H]cytidine and [3H]uridine into acid-soluble dCMP and a decreased incorporation of [3H]deoxycytidine into DNA. These observations indicated that the car cells had a larger pool size of deoxycytidine nucleotides and such an increase has indeed been found. © 1968.