The mutagenicity of hydrazine and some of its derivatives
| Autor: | R.F. Kimball |
|---|---|
| Rok vydání: | 1977 |
| Předmět: |
Methylhydrazine
Pyrimidine Alkylation Toxicology Coliphages chemistry.chemical_compound Genetics medicine Animals Crossing Over Genetic Biotransformation Carcinogen Genes Dominant Cell Nucleus Chromosome Aberrations Bacteria Chemistry Isoniazid DNA Plants Thymine Drosophila melanogaster Hydrazines Biochemistry Mutation Carcinogens Genes Lethal Cytosine Mutagens medicine.drug |
| Zdroj: | Mutation Research/Reviews in Genetic Toxicology. 39:111-126 |
| ISSN: | 0165-1110 |
| DOI: | 10.1016/0165-1110(77)90018-5 |
| Popis: | Hydrazine has a number of uses in industry as an antioxidant for boiler and cooling-tower water and as a source material for synthesizing a wide range of pharmaceuticals and plant growth inhibitors. Hydrazine can react with the pyrimidines in DNA to saturate the 5,6 double bond, especially of thymine; to form N4-aminocytosine; and to open up the pyrimidine ring with consequent loss of pyrimidines from DNA. It can act either directly with DNA or through intermediate radical reactions including the formation of H2O2. Some of the substituted hydrazines can also react in much the same way; others, especially the methyl derivatives, can act as alkylating agents to alkylate purines, primarily. H2O2 and the radical reactions are probably important for inactivating phage and transforming DNA treated in vitro. H2O2 is probably not important for mutagenesis in such systems, but it is likely that radical reactions are at low concentrations of hydrazine. At high concentrations direct reaction with the DNA probably predominates. The evidence suggests that both radical reactions and the direct amination of cytosine may be mutagenic for bacteria and phage treated within bacteria. Again, H2O2 does not seem to be important. The mutations produced by hydrazine are probably produced by direct mispairing at replication rather than by error-prone repair. It is not clear what the relative roles of the products of hydrazine action, N4-aminocytosine and 5,6-dihydrothymine, are in this process. Hydrazine produces mutations in higher plants and in Drosophila, but there are some unexpected features concerning time of detection and locus specificity that are not yet explained. The mutations produced by hydrazine seem to be mainly or entirely singlelocus changes. No dominant lethals are induced even though mutations are produced in bacteria in the host-mediated assay. No tests for chromosomal aberrations, other than those for dominant lethals, have been reported for this compound. Some of the derivatives of hydrazine (especially the methylhydrazine derivatives, but also some others) produce chromosomal aberrations and other chromosomal and nuclear effects. The methylhydrazine derivatives may act as alkylating agents, but the mechanism by which some of the other compounds, such as isoniazid, produce chromosomal aberrations is not clear. Hydrazine, isoniazid, and several alkyl derivatives have been reported to be positive in tests for carcinogenesis in laboratory rodents. There is as yet no evidence for carcinogenicity in humans for isoniazid, the only compound for which there is appreciable epidemiological data. The role of metabolic activation and other aspects of tissue specificity for carcinogenesis are still poorly understood. |
| Databáze: | OpenAIRE |
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