Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells

James K.V. Willson, James K.V. Willson, Byron H. Long, Subhas Chakrabarty, Diane E. Brattain, Michael G. Brattain, Michael G. Brattain, James K.V. Willson

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Abstract

BMY 25282, a newly designed analogue of mitomycin C (MMC), was assessed for its non-cross-resistant cytotoxic and biochemical action against MMC-resistant human colon carcinoma cells. The analogue has an amkJine substituted at position 7 of MMC and has a more efficient intracellular activation to its active species than MMC. In this study we demonstrated that BMY 25282 can overcome MMC resistance in a series of previously described human colon carcinoma cells resistant to MMC (Cancer Res., 44: 5880,1984). The non-cross-resistance of the analogue in the model was confirmed in vivo by treating tumor xenograft-bearing athymic mice with equitoxic closes of MMC or BMY 25282. We further investigated the formation of interstrand DNA cross-link (IDC) formation by BMY 25282 and MMC. MMC-sensitive cells contained 3 to 8 times as many IDCs as resistant colon carcinoma cells, while no significant differences in IDCs were found between the MMC-sensitive or -resistant cells incubated with BMY 25282. When MMC-sensitive or -resistant cells were exposed to the 70% inhibition concentration of either MMC or BMY 25282, no differences were seen with respect to IDC formation. These studies demonstrate that BMY 25282 is able to overcome MMC resistance in a series of human colon carcinoma cells and that IDC formation in the MMC-sensitive or -resistant cells parallels cytotoxicity for both MMC and the analogue.

Original languageEnglish (US)
Pages (from-to)5281-5286
Number of pages6
JournalCancer Research
Volume45
StatePublished - Nov 1 1985

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Willson, J. K. V., Willson, J. K. V., Long, B. H., Chakrabarty, S., Brattain, D. E., Brattain, M. G., Brattain, M. G., & Willson, J. K. V. (1985). Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells. Cancer Research, 45, 5281-5286.