DNA strand scission by the carbon radical derived from 2-phenyl-ethylhydrazine metabolism
- 1 January 1984
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 5 (6) , 781-784
- https://doi.org/10.1093/carcin/5.6.781
Abstract
Oxyhemoglobin catalyzed oxidation of the tranquilizing drug 2-phenylethylhydrazine induces single strand breaks (nicks) in the supercoiled pBR322 plasmid DNA. Spin-trapping studies have established a clear correlation between 2-phenylethyl radical yield and the DNA strand scission activity observed during 2-phenylethylhydrazine oxidation. The same correlation is obtained in the presence of active oxygen species scavengers or when the carbon radical is generated under anaerobic conditions by ferricyanide oxidation of the drug. In addition to DNA damage, the 2-phenylethylhydrazine turnover by oxyhemoglobin promotes destruction of the hemo-protein catalyst to as yet unidentified products. These results may be relevant for the expression of the mutagenic and carcinogenic properties of hydrazine derivatives.This publication has 12 references indexed in Scilit:
- Enzymatic activation of hydrazine derivatives. A spin-trapping study.Journal of Biological Chemistry, 1983
- Identification of N5-methyl-N5-formyl-2,5,6-triamino-4-hydroxypyrimidine as a major adduct in rat liver DNA after treatment with the carcinogens, N,N-dimethylnitrosamine or 1,2-dimethylhydrazineBiochemical and Biophysical Research Communications, 1983
- N-Phenylprotoporphyrin IX formation in the hemoglobin-phenylhydrazine reaction. Evidence for a protein-stabilized iron-phenyl intermediate.Journal of Biological Chemistry, 1982
- Skin Tumor-Promoting Activity of Benzoyl Peroxide, a Widely Used Free Radical-Generating CompoundScience, 1981
- Spin-trapping of free radicals formed during microsomal metabolism of ethylhydrazine and acetylhydrazineBiochemical and Biophysical Research Communications, 1981
- DNA-DAMAGING ACTIVITY INVIVO AND BACTERIAL MUTAGENICITY OF 16 HYDRAZINE DERIVATIVES AS RELATED QUANTITATIVELY TO THEIR CARCINOGENICITY1981
- Analysis of restriction fragments of T7 DNA and determination of molecular weights by electrophoresis in neutral and alkaline gelsJournal of Molecular Biology, 1977
- The mutagenicity of hydrazine and some of its derivativesMutation Research/Reviews in Genetic Toxicology, 1977
- Studies on the nucleotide arrangement in deoxyribonucleic acids IX. Selective degradation of pyrimidine deoxyribonucleotidesBiochimica et Biophysica Acta (BBA) - Specialized Section on Nucleic Acids and Related Subjects, 1964
- EQUILIBRIUM SEDIMENTATION OF MACROMOLECULES IN DENSITY GRADIENTSProceedings of the National Academy of Sciences, 1957