amphotericin-b and spirogermanium

Chinese hamster V79 cells were exposed to spirogermanium (SG), and their mitotic activity, population growth, plating efficiency, viability (dye exclusion), and clonogenicity were assayed. Mitotic frequency of cultures in SG decreased initially with increasing drug concentration and later plateaued at varying levels depending on drug concentration. Cultures continuously exposed to SG showed drug concentration-dependent growth inhibition, with no effect at 0.1-0.2 micrograms/ml and increasing toxicity above 0.5 microgram/ml. Cytolysis was enhanced by the simultaneous presence of amphoterocin B and by exposing cells to SG at 42 degrees C. Hypoxia protected cells from drug-induced lysis. The loss of membrane-intact cells was inversely related with population density at the time of drug exposure. Short exposures (up to 5 hours) at 20 micrograms/ml showed that cell killing was primarily through reduction of dye-excluding cells within a matter of hours and secondarily through loss of proliferative capacity. Prolonged drug contact (24 hours) at lower concentrations (1-5 micrograms/ml) accentuated the effect on clonogenicity. These results suggest that for clinical potency, prolonged drug contact may be beneficial.

Topics: Amphotericin B; Animals; Cell Division; Cell Line; Cell Survival; Chromosome Aberrations; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Germanium; Hot Temperature; Misonidazole; Mitosis; Mitotic Index; Organometallic Compounds; Spiro Compounds