Hormone-Dependent Stem-Cell Rat Leukemia Evoked by a Series of Feedings of 7,12-Dimethylbenz[a]anthracene

Abstract

A series of feedings of a lipid solution of 7,12-dimethylbenz[a]anthracene (DMBA) given biweekly by gastric intubation to juvenile rats of the Long-Evans strain elicited leukemias reproducibly, rapidly, and in high yields: females 82%; males 70%. The leukemias were predominantly of a single kind. A total of 56 consecutive leukemias were classified: stem-cell 55; myelogenous 1. The stem-cell leukemia grew exuberantly in sinusoids of liver, with diffuse replacement of the entire sinusoidal endothelium by leukemic stem cells. Allogeneic transplantation of whole blood of rats with advanced stem-cell leukemia to the subcutaneous tissue of the newborn resulted in sarcomas composed of undifferentiated stem cells at the injection site, together with secondary leukemia. Many of the stem-cell sarcomas and leukemias regressed rapidly and completely after hypophysectomy. A single feeding of large amounts of DMBA was specially toxic in male Sprague-Dawley rats; multiple feedings resulted in a high yield of stem-cell leukemias.