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- W2061878978 abstract "The cytological effects of DNA crosslinking agents, such as mitomycin C, nitrogen mustards, diepoxides, and dialkyl sulfonates were tested on 4-day chick embryos. At low dosage 12 of 14 of these agents produced cells morphologically identical to those found in naturally occurring areas of cellular death, e.g., the posterior necrotic zone (PNZ) and the presumptive interdigital spaces. Monofunctional analogs of the difunctional agents failed to produce the same type of cells at equivalent and higher doses. Other metabolic poisons, including actinomycin D, acridine orange, cycloheximide, colchicine, purine analogs, and cyanide were also negative; two exceptional compounds were daunomycin and hydroxyurea, both of which at moderate doses had the same cytological effects as the alkylating agents. Mitomycin C had the additional effect of producing severe quadrilateral phocomelia. An increased content of crosslinked DNA was detected in embryos treated with difunctional agents using the polyethylene glycoldextran phase separation procedure. Melting profiles and cesium sulfate equilibrium density gradients confirmed the bihelical nature of the renatured crosslinked DNA fractions. Examination of DNA isolated from presumptive interdigital spaces at several stages up to and including the stage of maximum cell death, revealed no increase in crosslinked DNA in these regions relative to controls. However, the number of effective crosslinks per cell could be well below the level of detection of the assay; thus the crosslinking hypothesis as a mechanism for programmed cell death in the chick embryo cannot be eliminated. Since crosslinking agents, daunomycin, and hydroxyurea are known to block the normal progress of the cell through its cycle, perhaps the cause of programmed cell death might be a similar block; other hypotheses are considered." @default.
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- W2061878978 date "1970-05-01" @default.
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- W2061878978 title "Studies on possible mechanisms of programmed cell death in the chick embryo" @default.
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- W2061878978 doi "https://doi.org/10.1016/0012-1606(70)90012-6" @default.
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