Effects of an antipsoriatic agent, dithranol, on mitochondrial and nuclear functions in yeast cells

Abstract

Respiration-deficient (petite) cells are much more resistant than respiration-competent (grande) cells of Saccharomyces cerevisae to the killing effect of dithranol at concentrations of 2 times 10-6 — 10 times 10-6M. The high proportions of cytoplasmic petites found in cultures of yeast treated at these concentrations are mainly due to this selective killing. However, at lower concentrations with little killing effect on grandes a strong net increase of the number of cytoplasmic petites was found. Dithranol can act as a photosensitizer. Results from photodynamic treatment indicate that the resistance of petites depends on their inability to take up dithranol. Cells grown in media with glycerol as carbon source were more resistant to the petite-inducing effect of dithranol than cells grown with glucose. Kinetic studies showed that both killing and petites can be induced by very short treatments, the maximal effect being obtained within 2–5 min. Reconstruction experiments showed that the dithranol available in the treatment solution was quickly bound to the cells. Dithranol was found to be much more effective than ethidium bromide in inducing petites by treatments under no-growth conditions in phosphate buffer. Mitotic recombination and gene conversion were not increased by treatment with dithranol in the dark. Light + dithranol gave a small increase of the frequency of mitotic gene conversion.