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 language | English (US) |
|---|---|
| Pages (from-to) | 5281-5286 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 45 |
| State | Published - Nov 1 1985 |
ASJC Scopus subject areas
- Oncology
- Cancer Research