Photosensitization by 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol: damage to erythrocyte membranes, Escherichia coli, and DNA.
The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near-ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions. A series of E. coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV. The presence of carotenoids did afford some protection to E. coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen. The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen. Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di-t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD). The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD. These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them. Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3. The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions. Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic. A light-dependent electron transfer to cytochrome c was obtained under argon but not under oxygen. Although induced mutations were not observed in the experiments with E. coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions. In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions. The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known.
Kagan
J
J
Department of Chemistry, University of Illinois, Chicago 60680.
Wang
T P
TP
Kagan
I A
IA
Tuveson
R W
RW
Wang
G R
GR
Lam
J
J
D000466:Alkadienes / Q000494:pharmacology*; D000480:Alkynes / Q000494:pharmacology*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D053279:Polyynes; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
D000466:Alkadienes; D000480:Alkynes; D011838:Radiation-Sensitizing Agents; C074977:2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol; D053279:Polyynes