A 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-beta-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.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013713:Teniposide / Q000494:pharmacology*
D011506:Proteins; D012313:RNA; D004247:DNA; D013713:Teniposide; D011034:Podophyllotoxin