Free radical activation of monomethyl and dimethyl hydrazines in isolated hepatocytes and liver microsomes

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Free Radic. Biol. Med.; (United States)

DOI:https://doi.org/10.1016/0891-5849(89)90152-4· OSTI ID:6459220

Albano, E; Tomasi, A; Goria-Gatti, L

Isolated hepatocytes and liver microsomes incubated with monomethyl-1,1 dimethyl- and 1,2 dimethyl-hydrazines produced free radical intermediates which were detected by ESR spectroscopy by using 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) as spin trapping agent. The spectral features of the spin adducts derived from all three hydrazine derivatives corresponded to the values reported for the methyl free radical adduct of 4-POBN. In the microsomal preparations inhibitors of the mixed function oxidase system and the destruction of cytochrome P450 by pretreating the rats with CoCl2 all decreased the free radical formation. Methimazole, an inhibitor of FAD-containing monoxygenase system, similarly decreased the activation of 1,1 dimethyl-hydrazine, but not that of monomethyl- and 1,2 dimethyl-hydrazines. The addition to liver microsomes of physiological concentrations of glutathione (GSH) lowered by approx. 80% the intensities of the ESR signals. Consistently, incubation of isolated hepatocytes with methyl-hydrazines decreased the intracellular GSH content, suggesting that GSH can effectively scavenge the methyl free radicals. The results obtained suggest that methyl free radicals could be the alkylating species responsible for the toxic and/or carcinogenic effect of methyl-hydrazines.

• Research Organization: Universita di Torino (Italy)
• OSTI ID: 6459220
• Journal Information: Free Radic. Biol. Med.; (United States), Journal Name: Free Radic. Biol. Med.; (United States) Vol. 6:1; ISSN FRBME
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOSYNTHESIS
CELL CONSTITUENTS
CHALCOGENIDES
DRUGS
ELECTRON SPIN RESONANCE
ENZYME INHIBITORS
ENZYMES
GLUTATHIONE
HYDRAZINE
LIVER CELLS
MAGNETIC RESONANCE
MAMMALS
METABOLISM
MICROSOMES
MIXED-FUNCTION OXIDASES
NITROGEN COMPOUNDS
NITROGEN OXIDES
ORGANIC COMPOUNDS
ORGANOIDS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
OXYGENASES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADICALS
RADIOPROTECTIVE SUBSTANCES
RATS
RESONANCE
RODENTS
SOMATIC CELLS
SYNTHESIS
TOXICITY
VERTEBRATES