Effect of vitamin A on methotrexate cytotoxicity in L1210 murine leukemia cells in culture.

Vitamin A (VA) protects the small intestine from methotrexate (MTX)-induced damage. However, before VA can be used as a remedy to protect cancer patients from MTX-induced damage to the intestine, it is essential to clarify whether or not it disturbs the antitumor activity of MTX. This study investigated the effect of VA on the antitumor activity of MTX in vitro in L1210 murine leukemia cells. The incorporation of [6-3H]-thymidine and [6-3H]-uridine, [5-3H]-uridine, and [4,5-3H]-leucine into DNA, RNA, and proteins, respectively, was examined to evaluate this effect. The incorporation of thymidine, the uridines, and leucine decreased dose-dependently in MTX-treated L1210 cells and profoundly in the MTX plus VA-treated L1210 cells, since VA itself had a cell-killing activity. Thus, MTX depressed the growth of L1210 cells dose-dependently and this depression was not affected by the presence of VA. The present study proved in L1210 murine leukemia cells in vitro that VA did not disturb the antitumor activity of MTX.