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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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

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Mitomycin
Colonic Neoplasms
Colon
Carcinoma
N(6)-((dimethylamino)methylene)mitomycin C
DNA
Heterografts
Nude Mice
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Willson, J. K. V., Willson, J. K. V., Long, B. H., Chakrabarty, S., Brattain, D. E., 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.

Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells. / Willson, James K.V.; Willson, James K.V.; Long, Byron H.; Chakrabarty, Subhas; Brattain, Diane E.; Brattain, Michael G.; Brattain, Michael G.; Willson, James K.V.

In: Cancer Research, Vol. 45, 01.11.1985, p. 5281-5286.

Research output: Contribution to journalArticle

Willson, JKV, Willson, JKV, Long, BH, Chakrabarty, S, Brattain, DE, Brattain, MG, Brattain, MG & Willson, JKV 1985, 'Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells', Cancer Research, vol. 45, pp. 5281-5286.
Willson JKV, Willson JKV, Long BH, Chakrabarty S, Brattain DE, Brattain MG et al. Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells. Cancer Research. 1985 Nov 1;45:5281-5286.
Willson, James K.V. ; Willson, James K.V. ; Long, Byron H. ; Chakrabarty, Subhas ; Brattain, Diane E. ; Brattain, Michael G. ; Brattain, Michael G. ; Willson, James K.V. / Effects of BMY 25282, a Mitomycin C Analogue, in Mitomycin C-resistant Human Colon Cancer Cells. In: Cancer Research. 1985 ; Vol. 45. pp. 5281-5286.
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