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Basic Sciences

Comparison of the Mechanism of Action of Busulfan with Hepsulfam, a New Antileukemic Agent, in the L1210 Cell Line

Diane Y. Pacheco, Nancy K. Stratton and Neil W. Gibson
Diane Y. Pacheco
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Nancy K. Stratton
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Neil W. Gibson
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DOI:  Published September 1989
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Abstract

1,7-Heptanediol disulfamate (hepsulfam, NSC 329680) is a new antileukemic agent with close structural similarity to busulfan. The mechanism of action of hepsulfam is not known and it has recently been entered into Phase I clinical trials by the National Cancer Institute. Waud et al. have recently shown that hepsulfam has good antitumor activity against mouse L1210 leukemia in vivo (Waud et al., Proc. Am. Assoc. Cancer Res., 29: 333, 1988). In contrast, busulfan was inactive against this model tumor system. In the present study, we have compared the in vitro cytotoxicity of hepsulfam with that of busulfan and we also examined the ability of these compounds to induce DNA damage in the L1210 leukemia cell line. Our results show that L1210 leukemia cells were 7-fold more sensitive to hepsulfam than busulfan. Only hepsulfam produced an appreciable quantity of DNA interstrand cross-linking in L1210 cells, with the peak of cross-link formation being delayed 12 h following a 2-h drug treatment. In contrast, both compounds also produced DNA-protein cross-linking, again with the formation of peak levels being delayed 6–12 h after drug treatment. At equimolar concentrations, hepsulfam produced a greater quantity of DNA interstrand cross-links and DNA-protein cross-links than busulfan. In contrast, busulfan produced a greater quantity of DNA-protein cross-links, when compared to hepsulfam at equitoxic concentrations.

Footnotes

  • ↵1 This work was supported in part by a gift to A. M. C. by The Women's Event, St. Louis, MO.

  • ↵2 To whom requests for reprints should be addressed.

  • Received November 28, 1988.
  • Revision received March 2, 1989.
  • Revision received May 22, 1989.
  • Accepted June 14, 1989.
  • ©1989 American Association for Cancer Research.
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September 1989
Volume 49, Issue 18
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Comparison of the Mechanism of Action of Busulfan with Hepsulfam, a New Antileukemic Agent, in the L1210 Cell Line
Diane Y. Pacheco, Nancy K. Stratton and Neil W. Gibson
Cancer Res September 15 1989 (49) (18) 5108-5110;

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Comparison of the Mechanism of Action of Busulfan with Hepsulfam, a New Antileukemic Agent, in the L1210 Cell Line
Diane Y. Pacheco, Nancy K. Stratton and Neil W. Gibson
Cancer Res September 15 1989 (49) (18) 5108-5110;
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