Abstract
The activity of two podophyllin derivatives, SPI-77 and SPG-827, was studied on normal and tumoral mammalian tissue culture cells. Rat normal fibroblasts, HeLa and Helius cells were cultivated in plasma clot with fluid medium in roller tubes; HeLa and KB cells were cultivated in monolayer; rat bone marrow was suspended in a fluid medium in stationary tubes. For every tissue these drugs produced a mitotic arrest in metaphase. Rat fibroblasts were more sensitive than tumor cells. The lowest concentrations that completely blocked cleavage ranged from 0.1 μg/ml for rat fibroblasts to 0.5 μg/ml for tumor cells. A mitotic arrest was observed after 1-2 hours’ treatment and it lasted until the drugs were present in the culture medium. When this culture medium was replaced with another without substances, blocked metaphases decreased and cells with few micronuclei were noted. It therefore appears that these podophyllin derivatives may act as spindle poisons, like colchicine. In fact, spindle fibres were not visible in the blocked metaphases and the chromosomes were scattered through the cytoplasm. These drugs acted on the cytoplasm too. Cells showed few cytoplasmic extrusions. Also on the bone marrow cells the metaphases block was evident after few hours’ treatment. Substances were active in all mieloid cells. Blocked metaphases seemed like C mitoses.
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