DNA repair and recovery in Escherichia coli after psoralen and angelicin photosensitization.
The correlation between DNA repair and recovery of biological functions was studied using three wild type strains of Escherichia coli and two skinphotosensitizing furocoumarins, psoralen and angelicin, which are well known specific reagents of the pyrimidine bases of DNA. In addition to mono-adducts psoralen is able to form a high number of inter-strand cross-links, while angelicin forms only mono-adducts. Both of these damages were repaired, in a short time, in the following way: at first DNA was cut into small pieces that were then rejoined into molecules of normal size, free from cross-links, while the furocoumarin residue was split from DNA almost quantitatively. Recovery of biological functions was studied performing photosensitization experiments in such a manner that the same amounts of psoralen or of angelicin were linked to bacterial DNA. DNA synthesis, tested just after the damage, was inhibited in a similar extent by both drugs. The same bacteria, however, showed a very different colony-forming capacity; angelicin was much less effective than psoralen with a D37 dose about 2.7 times higher. A similar picture was obtained studying DNA synthesis at different times after photosensitization: in the bacteria damaged by angelicin it was restored while no recovery was observed in cells photosensitized by psoralen. These results suggest that both mono-adducts and cross-links can be chemically repaired more or less in a quantitative measure, but that repair of cross-links in much less effective on cell recovery; this behaviour is very probably connected with the different repair mechanisms of mono-adducts and of cross-links.
D003374:Coumarins / Q000494:pharmacology*; D004260:DNA Repair / Q000187:drug effects; D004269:DNA, Bacterial / Q000096:biosynthesis; D004277:DNA, Single-Stranded / Q000378:metabolism; D004926:Escherichia coli / Q000528:radiation effects*; D005363:Ficusin / Q000494:pharmacology*; D011564:Furocoumarins; D007536:Isomerism; D008027:Light; D013936:Thymidine / Q000378:metabolism
D003374:Coumarins; D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D011564:Furocoumarins; C011659:angelicin; D005363:Ficusin; D013936:Thymidine