The phototoxicity of 8-methoxythionepsoralen and 6-methylthionecoumarin.
The phototoxicity of 8-methoxythionepsoralen (8-MOTP) and 6-methylthione coumarin (6-MTC) when activated by UV-A has been investigated using a variety of Escherichia coli strains, Haemophilus influenzae transforming DNA and Escherichia coli pBR322 plasmid DNA. The results demonstrate that 8-MOTP is a strictly oxygen independent photosensitizer that is about 500-fold less efficient in forming lesions leading to equivalent lethality than is the parent compound from which it is derived (8-MOP). As is true for 8-MOP, 8-MOTP is capable of inducing histidine independent mutations in E. coli and inactivating transforming DNA consistent with DNA being a target for lesions induced by this molecule in the presence of UV-A. 6-MTC is a strongly oxygen dependent photosensitizer activated by UV-A when tested with either E. coli cells or transforming DNA in contrast to the parent compound (6-methylcoumarin; 6-MC) which is not phototoxic when treated with UV-A. These results imply that the membrane may be an important target leading to lethality. 6-MTC in the presence of UV-A can inactivate pBR322 plasmid and Haemophilus influenzae transforming DNA activity in vitro suggesting that DNA is a potential target for this molecule when activated by UV-A.
Tuveson
R W
RW
Department of Microbiology, University of Illinois, Urbana 61801.
Wang
G R
GR
Becker
R S
RS
D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000528:radiation effects; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects / Q000528:radiation effects; D013871:Thiones / Q000138:chemical synthesis / Q000494:pharmacology*; D014307:Trioxsalen / Q000494:pharmacology; D014466:Ultraviolet Rays
D003374:Coumarins; D004269:DNA, Bacterial; D017319:Photosensitizing Agents; D013871:Thiones; C077526:6-methylthionecoumarin; C077525:8-methoxythionepsoralen; D008730:Methoxsalen; D014307:Trioxsalen