Reactivity of benzidine diimine with DNA to form N-(deoxyguanosin-8-yl)-benzidine
Benzidine diimine (BZDI), a reactive intermediate in the metabolic peroxidation of the carcinogen benzidine, has been reported to bind covalently to cellular proteins and nucleic acids. We have examined the nature of this interaction with DNA and have identified a major carcinogen-nucleoside adduct. BZDI (20-50 microM) reacted rapidly with DNA in vitro to give relatively high levels of covalently bound products (1-2 adducts/10(3) nucleotides; 30-45% yield). The binding was completely inhibited by addition of glutathione but was unaffected by acidic pH, air, free radical traps, or strong nucleophiles. Upon enzymatic hydrolysis of the BZDI-modified DNA and subsequent h.p.l.c., a major adduct was isolated and characterized by u.v., mass and proton magnetic resonance spectroscopy as N-(deoxyguanosin-8-yl)-benzidine. The identity of this adduct and its formation under various incubation conditions suggest a reaction mechanism that involves a simple deprotonation of the cationic diimine, formation of an electrophilic arylnitrenium ion, and covalent binding to guanine in the DNA.
- Research Organization:
- National Center for Toxicological Research, Jefferson, AR
- OSTI ID:
- 5858911
- Journal Information:
- Carcinogenesis; (United States), Journal Name: Carcinogenesis; (United States) Vol. 1; ISSN CRNGD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
ANIMALS
AROMATICS
AZAARENES
BENZIDINE
BIOCHEMICAL REACTION KINETICS
CATTLE
CHEMICAL BONDS
CHEMICAL REACTIONS
DECOMPOSITION
DNA
DNA ADDUCTS
DOMESTIC ANIMALS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROLYSIS
HYDROXY COMPOUNDS
IMINES
KINETICS
LABELLED COMPOUNDS
LYSIS
MAGNETIC RESONANCE
MAMMALS
METABOLISM
METABOLITES
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PURINES
REACTION INTERMEDIATES
REACTION KINETICS
RESONANCE
RUMINANTS
SOLVOLYSIS
TRITIUM COMPOUNDS
VERTEBRATES