Mutagenicity of cross-links and monoadducts of furocoumarins (psoralen and angelicin) induced by 360-nm radiation in excision-repair-defective and radiation-insensitive strains of Saccharomyces cerevisiae.
The furocoumarin psoralen can form both monoadducts and cross-links with DNA when combined with 360-nm radiation, whereas the analog angelicin can form monoadducts only. Psoralen plus 360-nm radiation causes mutation induction with a slope of 2 (log-log plot) for a radiation-insensitive strain, whereas angelicin action with 360-nm radiation displays a slope of unity. For a radiation-sensitive mutant defective in the excision-repair pathway, the actions of both angelicin and psoralen plus 360-nm radiation exhibit one-target kinetics, but at higher exposures psoralen plus 360-nm radiation assumes a slope of 2. The excision-repair-defective strain is considerably more sensitive to the furocoumarins plus 360-nm radiation than is the radiation-insensitive strain, both for killing and mutation induction. The simplest explanation for the data is that both cross-links and monoadducts, formed by furocoumarins with DNA when exposed to 360-nm radiation, are capable of inducing mutations, and that monoadducts are repaired 20 times more efficiently than cross-links by the excision-repair pathway.
D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics; D005363:Ficusin / Q000494:pharmacology*; D011564:Furocoumarins / Q000494:pharmacology*; D006238:Haploidy; D009152:Mutagenicity Tests; D009153:Mutagens; D010641:Phenotype; D011836:Radiation Tolerance; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
D004271:DNA, Fungal; D011564:Furocoumarins; D009153:Mutagens; D005363:Ficusin