Comparative study of early effects of epipodophyllotoxin derivatives and other cytostatic agents on mastocytoma cultures.

The effects of various cytostatic agents (mechlorethamine, 1-/3-D-arabinofuranosylcytosine, 6-mercaptopurine, methotrexate, colchicine, vincristine, a podophyllotoxin derivative, bleomycin, 1,2-bis(3,5-dioxopiperazin-1-yl)propane, the epipodophyllotoxin derivatives 4'-O-demethyl-1O-[4,6-O-2-thenylidene-ß-D-glucopyranosyl]epipodophyllotoxin and 4'-O-demethyl-1-O-[4,6-O-ethylidene-/3-D-glucopyranosyljepipodophyllotoxin, and X-rays) on cell prolifera tion, mitotic index, cellular DNA, RNA, and protein content and on the incorporation of their respective isotope-labeled precursors were studied in cultures of mastocytoma cell line P-815X2 during the first 6 hr of exposure to the various agents. Most of these agents exhibited effects compatible with their accepted mechanisms of action. An exception to this was the finding that 1-/3-D-arabinofuranosylcytosine de pressed the mitotic index to less than one-half of the con trol value within 90 min of drug addition; this effect is not compatible with an exclusive action in G, or S phase of the cell cycle, but it suggests an additional block in G-2. The two epipodophyllotoxin derivatives 4'-O-demethyl-1O-[4,6-O-2-thenylidene-/S-D-glucopyranosyl]epipodophyllotoxin and 4'-O-demethyl-1-O-]4, 6-O-ethylidene-0-D-gluco-