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Differences between Diploid and Heteroploid Cultured Mammalian Cells in Their Response to Puromycin Aminonucleoside^{1 ,2}

Department of Pathology, Jefferson Medical College, Philadelphia, Pennsylvania 19107

Treatment of several heteroploid cultured mammalian cell lines with suitably low concentrations of aminonucleoside resulted in partial depression of ribosomal RNA synthesis, shown by methylated albumin-Kieselguhr column chromatography of labeled nucleic acids, and a lowering of the cell RNA content. These RNA-depleted heteroploid cell lines containued to proliferate at control rates for several cell generations. Proliferation of diploid cell lines, on the other hand, was inhibited by aminonucleoside without depression in cell RNA content. Methylated albumin-Kieselguhr chromatography of nucleic acids showed that the inhibition of ribosomal RNA synthesis was quickly followed by the inhibition of syntheses of the other types of RNA and of DNA. The inhibitory effects of amino-nucleoside on both heteroploid and diploid cells were prevented by simultaneous treatment with inosine, suggesting that the action of the inhibitor was similar in the cells studied, since uptake of labeled aminonucleoside into the cell was not affected by the nucleoside.

These results show that the heteroploid cell has a greater capacity to proliferate when its rate of ribosomal RNA synthesis is depressed, probably because its ability to synthesize DNA has been freed from some of the controls present in diploid cells.

¹ Supported by USPHS Grants 2RO1 CA-05402-08 and 5TO1 GM-00813-06.

² Some of these results were reported previously in a preliminary form (30), and were presented at the 9th International Cancer Congress, Tokyo, Japan, October 23–29, 1966.

Received 1/17/68. Accepted 5/11/68.

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