Radiosensitization by misonidazole during recovery of cellular thiols following depletion by BSO or DEM.
V79 cells have been depleted of their endogenous thiols by treatment with 100 microM BSO for 16-18 hr, or 0.5 mM DEM for 1 hr. The recovery of cellular thiols after removal of the drugs was determined by h.p.l.c. or flow cytometry and the sensitizer enhancement ratio for 100 microM misonidazole was measured as a function of time after removal of the drugs. The SER of 1.2 for control (hypoxic) cells increased to 1.8 for BSO treated (hypoxic) cells and 2.2 for DEM treated ones, when thiol levels were below 10% of controls. The SER and thiol levels returned to control values within 5 hr of removing DEM. After BSO there was little change during the first 5 hr and then a gradual return to normal values by 24 hrs. The major fall in the SER after removal of the drugs occurred as the cellular thiols increased to 60% of control values.
McNally
N J
NJ
Cancer Research Campaign Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, England.
Soranson
J A
JA
D000693:Anaerobiosis; D000818:Animals; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D005978:Glutathione / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008920:Misonidazole / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D008298:Maleates; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; C014476:diethyl maleate; D005978:Glutathione