Effects of BMY 25282, a mitomycin C analogue, in mitomycin C-resistant human colon cancer cells.

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 amidine 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 doses 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.

• Authors: J K Willson, B H Long, S Chakrabarty, D E Brattain, M G Brattain
• Journal: Cancer research (Cancer Res) Vol. 45 Issue 11 Pt 1 Pg. 5281-6 (Nov 1985) ISSN: 0008-5472 [Print] United States
• PMID: 3931904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Mitomycins
• Mitomycin
• N(6)-((dimethylamino)methylene)mitomycin C
• DNA

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Biotransformation
• Cells, Cultured
• Colonic Neoplasms (drug therapy, pathology)
• DNA (metabolism)
• Drug Resistance
• Female
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred BALB C
• Mitomycin
• Mitomycins (metabolism, pharmacology)
• Neoplasm Transplantation
• Rats
• Transplantation, Heterologous