Genotoxic effect of caffeine in Yarrowia lipolytica cells deficient in DNA repair mechanisms

摘要

Caffeine is a compound that can exert physiological-beneficial effects in the organism. Nevertheless, there are controversies about its protective-antioxidant and/or its negative genotoxic effect. To abound on the analysis of the possible genotoxic/antioxidant effect of caffeine, we used as research model the yeast Yarrowia lipolytica parental strain, and mutant strains ( increment rad52 and increment ku80), which are deficient in the DNA repair mechanisms. Caffeine (5 mM) showed a cytostatic effect on all strains, but after 72 h of incubation the parental and increment ku80 strains were able to recover of this inhibitory effect on growth, whereas increment rad52 was unable to recover. When cells were pre-incubated with caffeine and H2O2 or incubated with a mixture of both agents, a higher inhibitory effect on growth of mutant strains was observed and this effect was noticeably greater for the Delta rad52 strain. The toxic effect of caffeine appears to be through a mechanism of DNA damage (genotoxic effect) that involves DSB generation since, in all tested conditions, the growth of Delta rad52 strain (cells deficient in HR DNA repair mechanism) was more severely affected.