Activation of neocarzinostatin chromophore and formation of nascent DNA damage do not require molecular oxygen.

Abstract:

: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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Kappen LS,Goldberg IH

doi

10.1093/nar/13.5.1637

subject

Has Abstract

pub_date

1985-03-11 00:00:00

pages

1637-48

issue

5

eissn

0305-1048

issn

1362-4962

journal_volume

13

pub_type

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