Potentiation of Growth‐inhibitory Activity of 9‐β‐d‐Arabinofuranosyladenine by 2′‐Deoxycoformycin in Human Cultured Cell Lines Derived from Leukemias and Lymphomas

摘要

Growth‐inhibitory activity of 2′‐deoxycoformycin (DCF) and 9‐β‐D‐arabinofuranosyladenine (Ara‐A) used either singly or in combination was assessed in 30 human cultured cell lines (seven T‐cell, nine B‐cell, five non‐T, non‐B, and nine myeloid cell lines) derived from leukemias and lymphomas. DCF had little activity even at 100 μM any of the cell lines, while Ara‐A had an obvious inhibitory effect on them, especially on non‐T, non‐B cell lines at 10 μM or less. Lymphoid cell lines were apparently more sensitive to the combined use of Ara‐A and DCF than myeloid cell lines. DCF potentiated the antiproliferative activity of Ara‐A not only in T‐cell lines with high adenosine deaminase (ADA) activity, but also in some other cell lines with low ADA activity. DCF was stable in the culture medium, but Ara‐A in the medium containing cultured cells was rapidly inactivated. DCF completely inhibited the inactivation of Ara‐A in the medium containing P12/ICH or NALM‐6, but not in the medium containing Daudi. This suggests that there is some unknown mechanism(s) of inactivation of Ara‐A other than ADA in Daudi, which was insensitive to Ara‐A in the presence of 1 μM DCF. The capacity of DCF to inhibit degradation of Ara‐A in the medium containing these cultured cells correlated with the level of Ara‐A sensitivity potentiated by DCF. In all seven T‐cell lines, seven of the nine B‐cell lines, all five non‐T, non‐B cell lines, and only three of nine myeloid cell lines, the IC50 value for Ara‐A decreased to 5 μM or less in the presence of 1 μM DCF. These results suggest that the combination of DCF and Ara‐A may be effective against various types of lymphoid malignancies and some myeloid leukemias.