The effect of vitamin a on the uptake of a water soluble and lipid soluble nitrosourea by the EMT6 mouse mammary tumor.

Recent reports have suggested that vitamin A, a recognized membrane-active agent, enhances the antitumor effect of certain lipid nitrosoureas in marine L1210 leukemia, when used as a pretreatment agent. A possible explanation may involve enhanced uptake or binding of the alkylating nitrosourea. This theory was tested by administering the lipid soluble ¹⁴C-CCNU and water soluble ¹⁴C-chlorozotocin (CZL), following vitamin A pretreatment (200 mg/kg), to mice bearing a solid tumor (EMT6 Mouse Mammary Tumor), and following the levels of radioactivity in the tumor versus time. A comparison of vitamin A pretreated mice with non-pretreated mice showed vitamin A to have no significant effect upon the incorporation of CLZ, and no enhancement of its antitumor activity, as measured by monitoring growth. On the other hand, the incorporation of the highly lipid soluble CCNU was significantly reduced by vitamin A pretreatment. CCNU, with or without vitamin A pretreatment, had little effect upon the growth of the tumor, while CLZ showed significant reduction in tumor size and growth. It appears that any enhancement of the antitumor activity of nitrosoureas by vitamin A does not involve increased uptake or prolonged binding of the alkylating agent.