Dihydrodiol Dehydrogenases and Polycyclic Aromatic Hydrocarbon Activation:  Generation of Reactive and Redox Active <i>o</i>-Quinones

Penning, T.M.; Burczynski, Michael E.; Hung, Chien Fu; McCoull, Kirsten D.; Palackal, Nisha; Tsuruda, Laurie S.

doi:10.1021/tx980143n

Cited by 437 publications

(360 citation statements)

References 89 publications

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“…Alteration of membrane structure can disrupt energy transduction and the activity of membrane-associated proteins (Sikkema et al, 1995). Additionally, metabolites of aromatic compounds, such as catechols and quinones, can be more toxic than the parent compound due to an increase in solubility, production of reactive oxygen species, or adduct formation with DNA and proteins (Penning et al, 1999;Schweigert et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Naphthalene metabolism and growth inhibition by naphthalene in Polaromonas naphthalenivorans strain CJ2

Pumphrey

Madsen

2007

Microbiology

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This study was designed to characterize naphthalene metabolism in Polaromonas naphthalenivorans CJ2. Comparisons were completed using two archetypal naphthalenedegrading bacteria: Pseudomonas putida NCIB 9816-4 and Ralstonia sp. strain U2, representative of the catechol and gentisate pathways, respectively. Strain CJ2 carries naphthalene catabolic genes that are homologous to those in Ralstonia sp. strain U2. Here we show that strain CJ2 metabolizes naphthalene via gentisate using respirometry, metabolite detection by GC-MS and cell-free enzyme assays. Unlike P. putida NCIB 9816-4 or Ralstonia sp. strain U2, strain CJ2 did not grow in minimal medium saturated with naphthalene. Growth assays revealed that strain CJ2 is inhibited by naphthalene concentrations of 78 mM (10 p.p.m.) and higher, and the inhibition of growth is accompanied by the accumulation of orange-coloured, putative naphthalene metabolites in the culture medium. Loss of cell viability coincided with the appearance of the coloured metabolites, and analysis by HPLC suggested that the accumulated metabolites were 1,2-naphthoquinone and its unstable auto-oxidation products. The naphthoquinone breakdown products accumulated in inhibited, but not uninhibited, cultures of strain CJ2. Furthermore, naphthalene itself was shown to directly inhibit growth of a regulatory mutant of strain CJ2 that is unable to metabolize naphthalene. These results suggest that, despite being able to use naphthalene as a carbon and energy source, strain CJ2 must balance naphthalene utilization against two types of toxicity.

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Section: Discussionmentioning

confidence: 99%

Naphthalene metabolism and growth inhibition by naphthalene in Polaromonas naphthalenivorans strain CJ2

Pumphrey

Madsen

2007

Microbiology

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“…PAHs can be converted to quinones via biotransformation, e.g. through reactions involving cytochrome P450 1A1, expoxide hydrolase and dihydrodiol dehydrogenase [26]. Quinones produce ROS and may be key compounds in PM toxicity along with transition metals [24,26].…”

Section: Generation Of Oxidative Stress By Ambient Particulate Pollutmentioning

confidence: 99%

“…through reactions involving cytochrome P450 1A1, expoxide hydrolase and dihydrodiol dehydrogenase [26]. Quinones produce ROS and may be key compounds in PM toxicity along with transition metals [24,26]. Redox cycling quinones undergo one-electron reductions by NADPH cytochrome P450 reductase to form semiquinones [27].…”

Section: Generation Of Oxidative Stress By Ambient Particulate Pollutmentioning

confidence: 99%

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Xia

Nel

2008

Free Radical Biology and Medicine

820

529

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Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The pro-inflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered NP may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effect of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed.

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“…The diol epoxide pathway is not the only mechanism for adduct formation from PAH. Depurinating adducts have been detected as a result of one electron oxidation, and adducts resulting from quinone formation have also been characterized (Casale et al, 2001;Penning et al, 1999). Adducts are also formed via 9-hydroxy-BaP-4,5-oxide (Ross and Nesnow, 1999).…”

Section: Adduct Structuresmentioning

confidence: 99%

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

et al. 2002

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It is estimated that cigarette smoking kills over 1 000 000 people each year by causing lung cancer as well as many other neoplasmas. p53 mutations are frequent in tobaccorelated cancers and the mutation load is often higher in cancers from smokers than from nonsmokers. In lung cancers, the p53 mutational patterns are different between smokers and nonsmokers with an excess of G to T transversions in smoking-associated cancers. The prevalence of G to T transversions is 30% in smokers' lung cancer but only 12% in lung cancers of nonsmokers. A similar trend exists, albeit less marked, in laryngeal cancers and in head and neck cancers. This type of mutation is infrequent in most other tumors aside from hepatocellular carcinoma. At several p53 mutational hotspots common to all cancers, such as codons 248 and 273, a large fraction of the mutations are G to T events in lung cancers but are almost exclusively G to A transitions in non-tobacco-related cancers. Two important classes of tobacco smoke carcinogens are the polycyclic aromatic hydrocarbons (PAH) and the nicotine-derived nitrosamines. Recent studies have indicated that there is a strong coincidence of G to T transversion hotspots in lung cancers and sites of preferential formation of PAH adducts along the p53 gene. Endogenously methylated CpG dinucleotides are the preferred sites for G to T transversions, accounting for more than 50% of such mutations in lung tumors. The same dinucleotide, when present within CpGmethylated mutational reporter genes, is the target of G to T transversion hotspots in cells exposed to the model PAH compound benzo[a]pyrene-7,8-diol-9,10-epoxide. As summarized here, a number of other tobacco smoke carcinogens also can cause G to T transversion mutations. The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.

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Dihydrodiol Dehydrogenases and Polycyclic Aromatic Hydrocarbon Activation: Generation of Reactive and Redox Active o-Quinones

Cited by 437 publications

References 89 publications

Naphthalene metabolism and growth inhibition by naphthalene in Polaromonas naphthalenivorans strain CJ2

Naphthalene metabolism and growth inhibition by naphthalene in Polaromonas naphthalenivorans strain CJ2

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers

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