Acetyl coenzyme A-dependent binding of carcinogenic and mutagenic dinitropyrenes to DNA

Journal Article · Sat Jun 01 00:00:00 EDT 1985 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/6.6.941· OSTI ID:5217207

Djuric, Z; Fifer, E K; Beland, F A

Dinitropyrenes are mutagenic and carcinogenic environmental pollutants found in diesel emissions and urban air particulates. In Salmonella typhimurium these compounds appear to be activated to mutagens by sequential nitroreduction and acetylation. The authors have examined whether or not similar activation pathways occur with mammalian nitroreductases and acetylases. When rat liver cytosol, NADPH and calf thymus DNA were incubated with (4,5,9,10(-3)H)1-nitropyrene, (4,5,9,10(-3)H)1,3-, 1,6- or 1,8-dinitropyrene very low levels of nitrated pyrene binding with DNA were detected. Addition of acetyl coenzyme A (AcCoA) to these incubations increased the binding of dinitropyrenes 20- to 40-fold while the binding of 1-nitropyrene was not affected. The extent of AcCoA-dependent binding of dinitropyrenes reflected the amount of nitroreduction, as measured by aminonitropyrene formation. However, the increase in binding of dinitropyrenes to DNA in the presence of AcCoA did not occur with dog liver cytosol which is known to be deficient in N-acetylases. These results suggest that cytosolic nitroreductases catalyze the formation of N-hydroxy arylamine intermediates which in the case of dinitropyrenes are converted to reactive N-acetoxy arylamines by cytosolic AcCoA-dependent acetylases.

• Research Organization: Univ. of Arkansas for Medical Sciences, Little Rock
• OSTI ID: 5217207
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 6; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLATION
ACYLATION
AIR POLLUTION
ANIMALS
AROMATICS
BACTERIA
BIOCHEMICAL REACTION KINETICS
BODY
CARCINOGENS
CHEMICAL REACTIONS
COENZYMES
CONDENSED AROMATICS
DIESEL ENGINES
DIGESTIVE SYSTEM
DNA
DOGS
ENGINES
ENZYME ACTIVITY
ENZYMES
EXHAUST GASES
FLUIDS
GASEOUS WASTES
GASES
GLANDS
HEAT ENGINES
HYDROCARBONS
IN VITRO
INTERNAL COMBUSTION ENGINES
KINETICS
LIVER
MAMMALS
METABOLIC ACTIVATION
MICROORGANISMS
MUTAGEN SCREENING
MUTAGENS
NITRO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
POLLUTION
PYRENE
RATS
REACTION KINETICS
RODENTS
SALMONELLA
SALMONELLA TYPHIMURIUM
SCREENING
VERTEBRATES
WASTES