Histologic and ultrastructural alterations of a xenografted human colon adenocarcinoma after treatment with titanocene dichloride.

The influence of the antitumor agent titanocene dichloride on the morphologic appearance of a heterotransplanted human colon adenocarcinoma was investigated. The first alterations in tumor cells manifested 12 h after administration of a single dose (40 mg/kg) and consisted of nuclear changes, such as chromatin condensation, enlargement of the nuclear envelope, structural changes of the nucleoli, and formation of segmented nuclei 12 h later; bundles of microfilaments, lipid droplets and inclusion bodies, often containing cellular debris, occurred in the cytoplasm. Intracytoplasmic virus particles of type A were detectable. They were obviously extruded into the extracellular space by a budding process and became extracellular virus particles of type C. Within 24 h after treatment, the mitotic index decreased from 2.5% to 0.3%. Whereas after administration of a single dose, recovery phenomena took place between 2 and 4 days, the severe destruction induced by 3-fold doses of titanocene dichloride (3 X 30 mg/kg), was apparently not reversible. These results confirm the tumor-inhibiting potency of titanocene dichloride against human colon adenocarcinoma and underline the discriminatory power of morphologic studies in the preclinical evaluation of cytostatic drugs against heterotransplanted human tumors.