Metabolism of 5-methoxypsoralen by Saccharomyces cerevisiae.
Incubation of methoxypsoralen (5-MOP) in the presence of diploid yeast cells (Saccharomyces cerevisiae) before UV-A exposure leads to an incubation-time dependent decrease of photoinduced genotoxic effects. The reduction in photoinduced genotoxicity is stronger in cells grown in the presence of 20% glucose and containing high levels of cytochrome P-450 than in cells grown in the presence of 0.5% glucose and containing undetectable levels of cytochrome P-450. Inhibition of P-450 activity by specific inhibitors, such as tetrahydrofuran and metyrapone, strongly affects the observed decrease in 5-MOP genotoxicity, indicating the involvement of P-450 in 5-MOP metabolism. As demonstrated by spectrophotometric and chromatographic (HPLC) analysis during incubation of 5-MOP with P-450 containing yeast cells, 5-MOP gradually disappears from the cell supernatant of the incubation mixture. The reduction in the chromatographic peak corresponding to 5-MOP is accompanied by the appearance of a new peak that probably corresponds to a metabolite. As shown by the use of P-450 specific inhibitors, the metabolite appears to be due to P-450 mediated 5-MOP metabolisation. Its UV absorption spectrum suggests an alteration of the pyrone moiety of the 5-MOP molecule.
Morichetti
E
E
Istituto di Mutagenesi e Differenziamento C.N.R., Pisa, Italy.
Ceragioli
C
C
Cundari
E
E
Del Carratore
R
R
Fiorio
R
R
Bronzetti
G
G
Averbeck
D
D
D000078223:5-Methoxypsoralen; D003434:Crossing Over, Genetic / Q000528:radiation effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000378:metabolism; D016296:Mutagenesis / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000528:radiation effects; D013056:Spectrophotometry, Ultraviolet; D014364:Tryptophan / Q000378:metabolism; D014466:Ultraviolet Rays
D065607:Cytochrome P-450 Enzyme Inhibitors; D007532:Isoleucine; D000078223:5-Methoxypsoralen; D014364:Tryptophan; D003577:Cytochrome P-450 Enzyme System; D005947:Glucose; D008730:Methoxsalen