Mitochondrial genetic damage induced in yeast by a photoactivated furocoumarin in combination with ethidium bromide or ultraviolet light

Abstract

Ethidium bromide (EB) and ultraviolet light (UV) in combination are known to produce a synergistic induction of "petite" mutants in yeast. Two other agents were combined with EB, 3-Carbethoxypsoralene (3 CPs) activated by 365 nm light or gamma rays. EB in combination with 3 CPs also resulted in an enhanced production of "petite" mutants. After the photoaddition of 3 CPs in exponential phase cells, recovery of the "petite" mutation during dark liquid holding was inhibited by the presence of EB producing an enhanced number of "petite" mutants. The behavior of mitochondrial antibiotic resistance markers after individual and combined treatments with EB and 3 CPs indicates a random loss of markers after EB and a preferential loss of a certain region for the 3 CPs photoaddition. The combination of the two agents leads to an additivity of total drug marker losses rather than a synergistic loss. The combination of EB with gamma rays produced no enhancement in "petite" induction. A combination of UV and 3 CPs showed a synergistic interaction for "petite" induction. These results indicate that the three agents, EB, UV and 3 CPs photoaddition may share a common repair step for mitochondrial lesions.

Effects of reduced mitochondrial DNA content on secondary mitochondrial toxicant exposure in Caenorhabditis elegans

“…However, this seems unlikely as we have previously shown that the concentrations of AfB 1 , paraquat and UVC used in the current study cause similar amounts of mtDNA damage [15, 53]. Finally, EtBr can act synergistically with UV light (365nm) [70]; however, we have previously shown that EtBr at this level does not exacerbate UVC (100–280nm)-induced mtDNA damage [35]. …”

Spontaneous and induced rho mutants of Saccharomyces cerevisiae: patterns of loss of mitochondrial genetic markers

“…The loss of mtDNA sequences has been studied in primary clones of rho mutants induced by different treatments: ethidium bromide (2,12,13), photoaddition of psoralen derivatives (12,14), UV irradiation (M. Heude and E. Moustacchi, Genetics, in press), mutation of nuclear genes (24), and phosphate starvation (26). The structure of the deletions can be determined genetically by using the numerous mitochondrial genetic markers now.available (9), including mutations which confer drug resistance (17,27) and mit mutations, which are specific defects in mitochondrial genes (1,3,10,15,20,23,25,28).…”