Apoptosis is induced by transforming growth factor-β1 within 5 hours in regressing liver without significant fragmentation of the DNA



In previous studies we showed that transforming growth factor-β1 induces apoptosis in hepatocyte cultures and regressing livers, the mature form being more potent than the transforming growth factor-β1 latency-associated protein. In this study we addressed the question of whether apoptosis can be induced within a short time after administration of transforming growth factor-β1. Five hours after a single intravenous injection of 25 μg mature transforming growth factor-β1/kg body weight, apoptosis is augmented ninefold in the regressing rat liver. A second preceding application induces no further augmentation. Transforming growth factor-β1 latency-associated protein shows no effect with either regimen. Morphological evaluation shows that 5 hr after injection of transforming growth factor-β1 nearly all apoptotic bodies are already engulfed by their neighbor cells. After homogenization of the transforming growth factor-β1-treated livers, the condensed apoptotic bodies are not destroyed and remain in the nuclear pellet. No DNA fragmentation into oligosomes could be detected after purification of the DNA from the nuclear pellet and application to conventional gel electrophoresis. Application of in situ nick translation, which allows detection of DNA single and double-strand breaks in individual apoptotic bodies, also revealed no substantial fragmentation of the DNA in apoptotic bodies. These studies show that transforming growth factor-β1 is able to induce apoptosis within a rather short time and also suggest that in vivo digestion of the DNA does not lead to chromatin condensation. (HEPATOLOGY 1993;18:1238-1246).