Interactions of BMS-181174 and radiation: studies with EMT6 cells in vitro and in solid tumors.

Abstract

N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C, (BMS-181174; previously designated as BMY25067) is a mitomycin C analog now in initial clinical trials. The experiments described in this report were performed to assess whether BMS-181174, like mitomycin C and porfiromycin, was selectively toxic to the hypoxic cells in solid tumors and might therefore prove valuable in combination with radiotherapy. In contrast to mitomycin C and porfiromycin, BMS-181174 was more toxic to aerobic EMT6 cells in vitro than to cells made acutely hypoxic. In vitro, BMS-181174 and radiation produced cytotoxicity compatible with either additive or slightly supra-additive cytotoxicity. In vivo, BMS-181174 was effective in killing cells in solid EMT6 tumors. The effects of regimens combining BMS-181174 and radiation in vivo were complex. Combinations of low doses of BMS-181174 plus a large dose of radiation were very effective in killing cells in solid tumors. However, the survival curve plateaued at high doses of BMS-181174, providing evidence for a subpopulation of tumor cells which were resistant to both BMS-181174 and radiation; this was hypothesized to be a hypoxic cell population.

• Authors: S Rockwell, M Kelley
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 39 Issue 1 Pg. 65-71 (Apr 1996) ISSN: 0167-8140 [Print] Ireland
• PMID: 8735495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Antineoplastic Agents, Alkylating
• Mitomycins
• Radiation-Sensitizing Agents
• Mitomycin
• N-7-(2-(nitrophenyldithio)ethyl)mitomycin C
• Porfiromycin

Topics

• Aerobiosis (drug effects)
• Animals
• Antibiotics, Antineoplastic (therapeutic use)
• Antineoplastic Agents, Alkylating (administration & dosage, therapeutic use)
• Cell Hypoxia (drug effects)
• Cell Survival (drug effects)
• Chemotherapy, Adjuvant
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Drug Resistance, Neoplasm
• Female
• Mammary Neoplasms, Experimental (drug therapy, radiotherapy)
• Mice
• Mice, Inbred BALB C
• Mitomycin (administration & dosage, therapeutic use)
• Mitomycins
• Neoplasm Transplantation
• Porfiromycin (therapeutic use)
• Radiation-Sensitizing Agents (administration & dosage, therapeutic use)
• Radiotherapy Dosage
• Skin Neoplasms (drug therapy, radiotherapy)
• Specific Pathogen-Free Organisms
• Tumor Cells, Cultured