Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Enhanced cytotoxicity of melphalan by prolonged exposure to nitroimidazoles: the role of endogenous thiols

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
The present study shows that a prolonged exposure of V-79 cells to a variety of nitroimidazoles (misonidazole, Ro-05-9963, Sr-2508, and MRT1-80) results in an enhanced cytotoxicity when these cells are subsequently exposed to melphalan. This process of enhanced malphalan toxicity occurred only when cells were pretreated with misonidazole under hypoxic conditions, suggesting that nitroreduction is necessary for chemosensitization as it is for increased radiosensitization. Different nitroimidazoles tested vary in the extent to which they sensitize cells to the subsequent action of melphalan. Repair from a misonidazole pretreatment is essentially complete by six hours. This study demonstrated that cysteamine could reduce the cytotoxicity of misonidazole and the enhancement of melphalan toxicity. This was an effect reversible with time and one implying similar mechanisms for the preincubation effect observed in vitro for radiation and chemotherapy agents.
Research Organization:
Coll. of Physicians and Surgeons of Columbia Univ., New York, NY
OSTI ID:
6864714
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8; ISSN IOBPD
Country of Publication:
United States
Language:
English