Specific inhibitors of the monooxygenase system of Saccharomyces cerevisiae modified the mutagenic effect of 4-nitroquinoline 1-oxide and the deethylation activity of the yeast.
A form of cytochrome P-450 is produced in Saccharomyces cerevisiae strain D7 during the logarithmic growth phase in 20% glucose liquid medium. This form was inhibited by metyrapone, tetrahydrofuran and by carbon monoxide, specific inhibitors of cytochrome P-450 in mammals. The inhibition was observed by means of the increase of the genetic activity of 4-nitroquinoline 1-oxide (4-NQO) on logarithmic growth phase cells of D7 strain, adding the inhibitors to the incubation mixture. 4-NQO is a strong direct mutagen on stationary phase cells that is detoxified by the monooxygenase system. The inhibition was measured by determining the decrease of the O-deethylation of 7-ethoxycoumarin in whole cells of yeast depending on different concentrations of inhibitors. A decrease of O-deethylation activity was found in the presence of tetrahydrofuran and metyrapone and this behaviour is typical of the cytochrome P-450 species induced by ethanol, as in mammals. Adding sodium phenobarbital to 0.5% glucose liquid medium, a form inhibited only by metyrapone was obtained. The presence of different inducible forms of cytochrome P-450 is evident.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D015660:7-Alkoxycoumarin O-Dealkylase; D003577:Cytochrome P-450 Enzyme System; D000431:Ethanol / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology*; D009600:Nitroquinolines / Q000494:pharmacology*; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*
D005663:Furans; D009153:Mutagens; D009600:Nitroquinolines; D000431:Ethanol; C018674:tetrahydrofuran; D015112:4-Nitroquinoline-1-oxide; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D008797:Metyrapone