Cytotoxicity of 5,6-dihydroxytryptamine in dimethylhydrazine-induced carcinomas of rat colon

Abstract

Male Sprague-Dawley rats were given weekly s.c. injections of 1,2-dimethylhydrazine (21 mg/kg) for 20 weeks. The injections were then discontinued, and, after an interval of 2 to 8 weeks, experimental animals were given i.p. injections of 5,6-dihydroxytryptamine (5,6DHT) at a dose of 40 mg/kg and sacrificed at intervals of 1, 2, 6, 16, and 48 hr later. Specimens of descending colon and carcinomas of the descending or transverse colon from sacrificed animals were examined using light microscopy and transmission electron microscopy. The results show that 5,6DHT at a dose of 40 mg/kg is cytotoxic to malignant colonic epithelial cells but not cytotoxic to adjacent nonmalignant colonic epithelial cells. In malignant colonic epithelial cells, ultrastructural changes in cytoplasmic membranes and mitochondria were evident at 1 hr after 5,6DHT treatment. At 6 hr after 5,6DHT treatment, light microscopy of sections of tumor showed areas of cell necrosis and disrupted tumor morphology. Sections of specimens taken 16 hr after treatment showed widespread destruction of malignant cells.