Summary
Polar solvents such as N,N-dimethyl acetamide (DMA) are known inducers of tumor cell differentiation in vitro. Nothing is known about their ability to induce differentiation in vivo. Using PCC4 AZArL murine embryonal carcinoma (EC) cells we examined the time course and dose response relationship of DMA induced EC differentiation in vitro. The effective continuous dose range of 0.1% to 0.15% gave a linear increase in differentiation index with the probability of attaining complete differentiation. EC tumors were raised subcutaneously in the flanks of strain 129 mice and DMA injected intraperitoneally at a dose calculated to attain tissue levels of between 0.1% and 0.15%. DMA induced significant differentiation primarily into neuroepithelium when compared to negative controls, but DMA was not as effective as retinoic acid. The extent of differentiation was dosage dependent, but the maximal dose of DMA was limited by toxicity mainly to the liver and lymphoid tissues. A graduated dosage schedule of DMA treatment reduced toxicity. These preliminary studies suggest that “differentiation therapy” with polar solvents such as DMA may be an effective adjunct to standard therapies.