Photobiological effects in Saccharomyces cerevisiae induced by the monofunctional furocoumarin 4,4′,6-trimethylangelicin (TMA) and the bifunctional furocoumarin 8-methoxypsoralen (8-MOP)

Abstract

Recently, the monofunctional furocoumarin 4,4′,6-trimethylangelicin (TMA) has been proposed for photochemotherapeutic use. In order to assess its genotoxic potential, the photobiological (genetic) effects of TMA were studied in a diploid strain of Saccharomyces cerevisiae (D7) and compared to those of the bifunctional furocoumarin 8-methoxypsoralen (8-MOP). At equimolar concentrations, the induction of lethal effects by TMA in the presence of equal 365-nm radiation was higher than that exerted by 8-MOP. TMA was also more active than 8-MOP in inducing nuclear events such as nuclear reverse mutation and mitotic recombination (crossing-overs and gene conversion) per unit dose of 365-nm radiation.At equal survival, however, TMA was less efficient in inducing reverse mutation and crossing-over, showing the same activity as 8-MOP in the induction of gene conversion. TMA was more active than 8-MOP in the induction of cytoplasmic ‘petite’ mutations per unit dose of 365-nm radiation and per viable cell.The high photobiological activity of this monofunctional furocoumarin is mainly related to its strong DNA photobinding but also to the type of monoaddition induced, to the sequential distribution in DNA and to the generation of active forms of oxygen.