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Action of Camptothecin on Mammalian Cells in Culture

L. H. Li, T. J. Fraser, E. J. Olin and B. K. Bhuyan
L. H. Li
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T. J. Fraser
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E. J. Olin
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B. K. Bhuyan
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DOI:  Published December 1972
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Summary

Camptothecin (CN) is active against several experimental tumors and has also been studied clinically. We report here the effect of CN on L1210 cells and asynchronous and synchronous DON cells in culture.

CN was toxic both to L1210 cells (0.06 µg/ml, 2-hr exposure) and DON cells (0.15 µg/ml, 1-hr exposure), and it inhibited DNA and RNA synthesis more than it inhibited protein synthesis. CN was more cytotoxic to DON cells in S phase than cells in G1 or G2, although it inhibited DNA and RNA synthesis of L1210 cells and asynchronous DON cells almost equally. When asynchronous DON cells were exposed to CN for 30 min and CN was then removed, RNA synthesis was no longer significantly inhibited, but the inhibition of DNA synthesis persisted. The survival patterns of synchronous DON cells were closely related to DNA synthesis inhibition but not to RNA synthesis inhibition. These results collectively suggested that the marked effect of CN on DNA synthesis appeared to be one of the primary determinants of its cytotoxicity. Since no significant effect was observed on the enzymes involved in DNA synthesis, DNA synthesis inhibition by CN may be in part due to its effect on the DNA template. The interaction between CN and DNA was detected by melting point determinations. CN did not block the progression of mitotic cells into S phase. At 100 µg/ml, CN prevented the progression of S phase cells into G2; at 1 µg/ml, some cells did leave S and proceeded into G2. Cells in G2 were blocked from moving into mitosis even at 0.01-µg/ml doses of CN. Thus, the progression of late S or early G2 cells into mitosis was most sensitive to the drug.

Footnotes

  • ↵1 This investigation was supported in part by Contract PH 43-NCI-68-1023 with Drug Research and Development, National Cancer Institute, NIH, Bethesda, Md. 20014.

  • Received June 30, 1972.
  • Accepted August 23, 1972.
  • ©1972 American Association for Cancer Research.
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December 1972
Volume 32, Issue 12
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Action of Camptothecin on Mammalian Cells in Culture
L. H. Li, T. J. Fraser, E. J. Olin and B. K. Bhuyan
Cancer Res December 1 1972 (32) (12) 2643-2650;

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Action of Camptothecin on Mammalian Cells in Culture
L. H. Li, T. J. Fraser, E. J. Olin and B. K. Bhuyan
Cancer Res December 1 1972 (32) (12) 2643-2650;
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