Conversion of malignant murine embryonal carcinomas to benign teratomas by chemical induction of differentiation in vivo.

PCC4azal embryonal carcinoma tumors were grown in strain 129 mice by s.c. transplantation. When palpable, the tumors were treated with a combination of retinoic acid and dimethylacetamide. In vitro, this embryonal carcinoma cell line shows minimal spontaneous differentiation and is exquisitely sensitive to retinoic acid and/or dimethylacetamide induction of differentiation. Ten daily 20-microliter intratumor injections of a solution of 10 mg retinoic acid per ml of dimethylacetamide resulted in nearly complete induction of morphological differentiation mainly into neuroepithelial and glandular derivatives. Control tumors showed minor spontaneous differentiation. Differentiation was associated with decreased tumor growth rate, decreased mitotic index, decreased extent of necrosis, and increased survival time of the hosts. In 4 of 18 cases, long-term survival of the hosts was effected by a complete differentiation of the malignant embryonal carcinoma tumors into benign teratomas. Retinoic acid:dimethylacetamide was also effective in inducing differentiation with the same dosage and schedule when administered systemically, i.e., i.p. or s.c.