Genetic effects and repair of DNA photo-adducts induced by 8-methoxypsoralen and homopsoralen (pyranocoumarin) in diploid yeast.
The relationship between DNA mono- and di-adducts and genetic effects induced by the pyranocoumarin 8,8-desmethylxanthyletine (homopsoralen) HP and 365 nm radiation (UVA) was investigated in the diploid yeast strain D7 (Saccharomyces cerevisiae) taking 8-methoxypsoralen (8-MOP) as a reference compound. The number of DNA cross-links (CLs) induced was determined using alkaline step elution analysis. The induction and removal of total photo-adducts was followed using radioactively labelled compounds. HP showed the same photobinding capacity as 8-MOP. As a function of UVA dose, it was less effective than 8-MOP for the induction of CLs and genetic effects. However, as a function of CLs induced, HP was shown to be more effective for the induction of lethal effects and mitotic recombination than 8-MOP but equally effective for the induction of mutations. The results suggest that, although CLs are recognized as genetically effective lesions, at a given number of CLs, HP induced mono-adducts efficiently contribute to the induction of lethal effects and mitotic recombination but less to the induction of mutations. Using a re-irradiation protocol, HP was brought to yield the same relative amounts of CLs at the same number of total adducts as single UVA exposures with 8-MOP. In these conditions, mutation induction and the kinetics for the removal of photo-adducts were the same for both agents indicating that not only the removal of adducts but also mutation induction are highly dependent on the relative level of CLs induced.
Averbeck
D
D
Institut Curie-Biologie, CNRS UA 1292, Paris, France.
Cundari
E
E
Dardalhon
M
M
Dall'Acqua
F
F
Vedaldi
D
D
D004260:DNA Repair; D004271:DNA, Fungal / Q000187:drug effects* / Q000528:radiation effects; D004171:Diploidy; D011564:Furocoumarins / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008730:Methoxsalen / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D011564:Furocoumarins; C058611:homopsoralen; D008730:Methoxsalen