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Poly(deoxyadenylic-deoxythymidylic acid) damage by radiolytically activated neocarzinostatin

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00323a003· OSTI ID:5565564
The anaerobic reaction of poly(deoxyadenylic-deoxythymidylic acid) with neocarzinostatin activated by the carboxyl radical CO/sub 2/-, an electron donor generated from gamma-ray radiolysis of nitrous oxide saturated formate buffer, has been characterized. DNA damage includes base release and strand breaks. Few strand breaks are formed prior to alkaline treatment; they bear 3'-phosphoryl termini. In contrast, most (66%) of the base release occurs spontaneously. DNA damage is highly (95%) specific for thymidine sites. Neither DNA-drug covalent adduct nor nucleoside 5'-aldehyde, which are major products in the DNA-nicking reaction initiated by mercaptans and oxygen, is formed in this reaction. Data are presented to show that the CO/sub 2/(-)-activated neocarzinostatin intermediate is a short-lived free radical able to abstract hydrogen atoms from the C-1' and C-5' positions of deoxyribose. Attack occurs mostly (68%) at the C-1' position, producing a lesion whose properties are consistent with those of (oxidized) apyrimidinic sites.
Research Organization:
Harvard Medical School, Boston, MA
OSTI ID:
5565564
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 24:2; ISSN BICHA
Country of Publication:
United States
Language:
English