QUANTITATIVE MICRODENSITOMETRIC AND AUTORADIOGRAPHIC STUDY OF THE EFFECT OF 4'-DEMETHYL-EPIPODOPHYLLOTOXIN-BETA-D-THENYLIDENE GLUCOSIDE (VM-26) ON THE CELL-CYCLE OF CULTURED FIBROBLASTS

The effect of 4′-demethyl-epipodophyllotoxin-β-d-thenylidene glucoside (VM-26), a semi-synthetic derivative of podophyllotoxin, on the cell cycle was studied with chick embryo fibroblasts cultivated in vitro. DNA, RNA and protein content, as well as NADH-diaphorase activity were determined by quantitative microdensitometry and cytofluorometry. The incorporation of [3H]thymidine and [3H]leucine into DNA and proteins were analysed by autoradiography. These metabolic data correlated with morphological observation showed that VM-26 blocks the cell cycle at different moments of its kinetics depending on both the dose and the time exposure. NADH-diaphorase activity is the first to be affected, then biochemical changes (involving the metabolism of RNA and proteins) and morphological alterations (especially of mitochondria) follow. This suggests that VM-26 may act primarily upon the mechanism of respiration of the cell. © 1979 Chapman and Hall Ltd.