Inducibility of NADPH cytochrome c (P-450) reductase in yeast: role in the bioactivation of nitroimidazo(2,1-b)thiazoles.

Nine nitroimidazo(2,1-b)thiazoles were tested for their ability to induce convertants, revertants and mitotic recombinants on growing and stationary phase cells of Saccharomyces cerevisiae D7 strain. All compounds were genetically active only on cells from the logarithmic growth phase (from a 20% glucose medium), inducing dose-related increases in conversion and reversion frequencies. The addition of S9 microsomal fraction to stationary phase cells gave positive results at levels of doses 10-100 times lower than that used with growing cells. NADPH cytochrome c (P-450) reductase activity was determined in order to compare the capability of hepatic and yeast microsomes in bioactivating the test compounds. Results showed that nitroreductive enzymes are inducible by conditions supporting growth. The greater sensitivity of the treatment with external metabolic activation could be due to the greater content (about 14-fold) of NADPH cytochrome c-reductase activity in hepatic microsomes.