Activation of neocarzinostatin chromophore and formation of nascent DNA damage do not require molecular oxygen.
Thiol-activated neocarzinostatin chromophore abstracts tritium from the 5', but not from the 1' or 2' positions of deoxyribose in DNA and incorporates it into a stable, non-exchangeable form. The abstracted tritium remains covalently associated with the chromophore or its degradation product after treatment with acid or alkali, respectively. Drug activation and the consequent hydrogen abstraction reaction, presumably generating a carbon-centered radical at C-5', do not require molecular oxygen but have a dose-dependent relation with thiol. Under aerobic conditions, where base release and DNA strand breaks with nucleoside 5'-aldehyde at the 5'-ends are produced, hydrogen abstraction from C-5' parallels these parameters of DNA damage. It is possible to formulate a reaction scheme in which the carbon- centered radical at C-5' is an intermediate in the formation of the various DNA damage products found under both aerobic and anaerobic conditions.
Kappen
L S
LS
Goldberg
I H
IH
D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D010582:Bacteriophage lambda / Q000235:genetics; D004260:DNA Repair; D004279:DNA, Viral / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D010100:Oxygen; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D009353:Zinostatin / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D004279:DNA, Viral; D013438:Sulfhydryl Compounds; D014316:Tritium; D009353:Zinostatin; D010100:Oxygen