In vitro cytotoxicity of hepsulfam against human tumor cell lines and primary human tumor colony forming units

Stem Cells
M V MarshallD D Von Hoff

Abstract

Hepsulfam (sulfamic acid 1,7-heptanediyl ester, NSC 329680) is an alkylating agent currently in Phase I clinical trials. Hepsulfam was developed as an analog of busulfan, an alkylating agent that is used to treat patients with chronic myelogenous leukemia and for marrow ablation prior to bone marrow transplantation. The objective of this study was to identify the spectrum of human tumor cells that were sensitive to hepsulfam. The following three cytotoxicity assays were employed to evaluate the in vitro cytotoxic potential of hepsulfam: 1) primary human tumors were exposed to three levels of hepsulfam for a one hour or continuous exposure, and growth in soft agar was determined; 2) human non-tumor cells and tumor cell lines were compared in an assay that measured the conversion of 14C-glucose to 14CO2 as an index of viability; and 3) the toxicity of hepsulfam to hematopoietic progenitor cells was determined in a progenitor cell colony forming assay. Cytotoxicity was not observed for human tumor cells following one hour hepsulfam exposures; in contrast, marked dose-dependent cytotoxicity was observed with continuous exposures. In human tumor cell lines, the cytotoxicity of hepsulfam was compared directly with busulfan at equimol...Continue Reading

References

Mar 1, 1987·International Journal of Cell Cloning·U HanauskeD D Von Hoff

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Citations

Jan 1, 1995·Investigational New Drugs·M V MarshallJ G Kuhn
Aug 2, 2001·Leukemia·Z HassanE Hellström-Lindberg
Jul 22, 2008·Blood·Sabina I SwierczekJosef T Prchal
Sep 16, 2009·Molecular Nutrition & Food Research·Astrid PetermannFrank-D Böhmer
Apr 17, 2007·Blood·George L Chen, Josef T Prchal

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