Poly(deoxyadenylic-deoxythymidylic acid) damage by radiolytically activated neocarzinostatin.
The anaerobic reaction of poly(deoxyadenylic-deoxythymidylic acid) with neocarzinostatin activated by the carboxyl radical CO2-, 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 CO2(-)-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.
Favaudon
V
V
Charnas
R L
RL
Goldberg
I H
IH
D000903:Antibiotics, Antineoplastic / Q000528:radiation effects; D001059:Apoproteins; D005609:Free Radicals; D005720:Gamma Rays; D010100:Oxygen; D011067:Poly dA-dT; D011089:Polydeoxyribonucleotides; D011854:Radiochemistry; D009353:Zinostatin / Q000528:radiation effects
D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D005609:Free Radicals; D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; D009353:Zinostatin; D010100:Oxygen