Enhancement of the Antitumor Effects of 1,3-Bis(2-Chloroethyl)-1-Nitrosourea and Cyclophosphamide by Vitamin A<xref ref-type="fn" rid="FN2">2</xref>

Abstract

Vitamin A alcohol enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to a considerable extent and of cyclophosphamide to a lesser degree in murine L1210 leukemia. Enhancement was maximal when vitamin A alcohol was given parenterally 3–6 hours before the carcinostatic agent. The observed enhancement was somewhat specific for the nitrosoureas, since less effect was seen when other alkylating agents and antimetabolites were studied. Direct observation of leukemic cells and ancillary experiments on red blood cells suggest that enhancement was secondary to a vitamin A-BCNU interaction within tumor cell membranes, leading to irreversible and lethal membrane alterations. The doses of vitamin A used appear tolerable for humans.