Invasive Tumors Induced in Rats with Actinomycin D

Multiple i.p. injections of actinomycin D induced invasive, transplantable tumors, but actinocylgramicidin S did not. The mechanism of oncogenesis by actinomycin D may be dependent upon the intact peptide lactone moieties, since the analog, actinocylgramicidin S, which contains the universal actinomycin chromophore but does not bind with DNA, was not oncogenic. Most of the actinomycin-induced tumors displayed a variety of gross features and histological patterns. Grossly, the tumors appeared as multiple, gray or yellow, firm, irregular, predunculated, or sessile nodules 2 to 10 mm in diameter attached to peritoneum, mesentery, and serosal surfaces of the abdominal viscera. In addition to this surface growth, there was invasion into the muscularis of the bowel and, occasionally, infiltration between pancreatic lobules as well as into portal tracts of the liver. Microscopically, each tumor contained a variety of histological patterns; in most instances, a fibrosarcomatous appearance predominated but, within the same tumors, there were areas resembling hemangioma, dilated cysts, an alveolar pattern, osseous foci, and, in peripancreatic tissue, adenocarcinoma. Because of the prominent surface growth and the variation in histology, the tumors were interpreted tentatively as mesotheliomas. Preliminary electron microscopic examination revealed that the tumors had ultrastructural features similar to those reported in mesotheliomas in humans. No insulin-like activity was detected. The solid tumor and ascites form were transplantable through several generations.