Progressions of a Reticulum-Cell Sarcoma of the Mouse In Vivo and In Vitro

Abstract

A histiocytic neoplasm, induced by methylcholanthrene in a DBA/2 mouse and adapted to ascites form, has been observed in serial mouse transfer and in continuous culture for 2 years. In vivo, the neoplasm showed a minor amount of morphologic progression toward a less well-differentiated histiocytic form. In vitro, morphologic progression was marked by the appearance of cells with single or multiple giant nuclei. Ascites tumors resulting from inoculation of cultures into mice 11 months after explantation showed greater morphologic change than the tumors carried continuously in mice during the same period. Changes consisted in increased pleomorphism, the occurrence of numerous giant cells, and the loss of distinctive histiocytic features. Ascites tumors derived from cultures at 11 months showed a nearly pure hypotetraploid population, compared with a predominantly hyperdiploid population in the serially mouse-passed line at comparable time. Mitoses in cells in culture after 24 months showed chromosome numbers predominantly in the near-diploid range. Metacentric chromosomes were found both in long-term cultures and in ascites tumors derived from cultures, but not in the serially mouse-passed line. In continuous mouse passage the ascites tumor showed at the 15th and 69th transfers nearly equal virulence. After 8 and 11 months in continuous culture, the ascites tumors derived from these cultures showed a marked decrease of virulence. After 11 months or more in culture, inoculums of 10⁶ culture cells into mice rarely resulted in tumor production. Mechanisms of origin of the observed changes of latent period, virulence, and tumor-producing ability are discussed.