Mutagenic and genotoxic potential of nitrated polyaromatic hydrocarbons in combustion byproduct mixtures

• Main Author: Pritchett, Blair, 1970-
• Other Authors: Memorial University of Newfoundland. Dept. of Biochemistry
• Format: Thesis
• Language: English
• Published: 1999
• Subjects: Combustion gases > Toxicology; Mutagens; Genetic toxicology; Newfoundland studies; University of Newfoundland
• Online Access: http://collections.mun.ca/cdm/ref/collection/theses3/id/61141

Thesis (M.Sc.)--Memorial University of Newfoundland, 2000. Biochemistry Bibliography: leaves 114-122 The combustion of hydrocarbon fuels generates a considerable amount of reaction byproducts, some of which are mutagenic and DNA-reactive nitro-polyaromatic hydrocarbons. This mutagenic action is generally indirect, such that the compounds require metabolic activation for the exertion of their toxic effect. -- Used motor oil extracts prove more mutagenic than crude oil extracts in the Ames Salmonella assay for mutagenicity. This mutagenic effect is enhanced by the presence of a rat liver microsomal and cytosoiic protein preparation, as well as by the use of a bacterial strain enriched in O -acetylase activity. The mutagenic response is diminished in a bacterial strain that is deficient in bacterial nitroreductase. These data implicate nitrocompounds as principal agents in the overall mutagenicity of crankcase oil extracts. Crankcase oil extracts prove to be good substrates for nitroreductase enzyme activity in vitro. The effectiveness as a substrate of nitroreductase enzyme(s) also seems to correlate with the mutagenicity as measured in the Ames Salmonella assay. The measured nitroreductase activity exhibits no appreciable difference when NADH or NADPH is used as the reaction cofector. -- The activity cf nitroreductase enzymes can produce reactive oxygen species such as hydroxyl radicals (OH), which can generate single strand nicks in DNA This effect can be initiated by the metabolism of nitrated polynuclear aromatic hydrocarbons by mammalian liver enzymes. 1-nitropyrene and crankcase oil extracts are shown here to be capable of producing such nicks in the DNA of the plasmid pBR322.