Metabolic activation of nitropyrenes and diesel particulate extracts

Journal Article · Sun Jul 01 04:00:00 EDT 1990 · Research Report Health Effects Institue; (USA)

OSTI ID:6055391

Jeffrey, A M; Santella, R M; Wong, D; Hsieh, L L; Heisig, V; Doskocil, G; Ghayourmanesh, S ^[1]

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1. Columbia Univ., New York, NY (USA)

The aim of this research was to investigate the possible risks of genotoxicity associated with human exposure to diesel engine emissions. We sought to identify and evaluate the critical components of such emissions by using a variety of short-term biological systems. Adducts formed between benzo(a)pyrene and DNA in several short-term test systems have been thoroughly investigated. Although benzo(a)pyrene has long been used as an index of the potential carcinogenicity of polycyclic aromatic hydrocarbon mixtures and is present in diesel engine emissions, it may not be the best measure of the carcinogenicity of these emissions if, indeed, they are confirmed to exert such an effect in humans. Certain nitroarenes, known to be present in diesel particulate extracts, are very potent mutagens in the Ames assay. The major adducts formed in Salmonella typhimurium with 1-nitropyrene and 1,8-dinitropyrene have been identified. We undertook, therefore, a comparison of the DNA adducts formed between 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, and 1,8-dinitropyrene and cellular DNA in various systems, including human bronchial segments, in rabbit lung and trachea, and mouse embryo fibroblast C3H/10T1/2 cells, with those reported to be formed in S. typhimurium. In these studies, we administered radiolabeled nitropyrenes, analogous to the treatments previously employed for testing benzo(a)pyrene, and isolated and digested the modified DNA. We then compared elution times, by high-pressure liquid chromatography, of the radioactive adducts with synthetic standards. Not all combinations of exposures were undertaken, since the direction of the investigations changed to include studies on adducts formed in animals exposed to diesel engine emissions themselves. Of the samples studied, metabolism of 1-nitropyrene was most evident in the human bronchial tissue.

• OSTI ID: 6055391
• Journal Information: Research Report Health Effects Institue; (USA), Journal Name: Research Report Health Effects Institue; (USA) Vol. 34; ISSN RRHIE
• 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.
ADDUCTS
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
BODY
BRONCHI
CONDENSED AROMATICS
DIESEL ENGINES
DNA ADDUCTS
ENGINES
EXHAUST GASES
FLUIDS
GASEOUS WASTES
GASES
GENETIC EFFECTS
HEAT ENGINES
HYDROCARBONS
INTERNAL COMBUSTION ENGINES
LUNGS
MAMMALS
MAN
METABOLIC ACTIVATION
MICE
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PRIMATES
PYRENE
RABBITS
RESPIRATORY SYSTEM
RODENTS
TRACHEA
VERTEBRATES
WASTES