8-Hydroxydeoxyguanosine in DNA from TPA-Stimulated Human Granulocytes

Birnboim, H.C.; Maidt, Lindsay; Raynor, Tina; Floyd, Ronald A.

doi:10.3109/10715769409147508

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…In coincubations exposed to B Parallel analysis of oxidative DNA damage showed that stimulation by phorbol ester caused enhanced ratios of 8-oxodG/dG in PMN, which is in agreement with previous observations (18,23) but in contrast to a recent study (24). In coincubations exposed to B Parallel analysis of oxidative DNA damage showed that stimulation by phorbol ester caused enhanced ratios of 8-oxodG/dG in PMN, which is in agreement with previous observations (18,23) but in contrast to a recent study (24).…”

Section: Discussionsupporting

confidence: 92%

Neutrophils Amplify the Formation of DNA Adducts by Benzo[a]pyrene in Lung Target Cells

Borm¹,

Knaapen²,

Schins³

et al. 1997

Environmental Health Perspectives

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Inflammatory cells and their reactive oxygen metabolites can cause mutagenic effects in lung cells. The purpose of this study was to investigate the ability of activated neutrophils to modulate DNA binding of benzo[a]pyrene (B[a]P), a known carcinogen, in lung target cells. Equivalent numbers of rat lung epithelial cells (RLE-6TN cell line) and freshly isolated human blood neutrophils (PMN) were coincubated in vitro for 2 hr after addition of benzo[a]pyrene (0.5 microM) or two of its trans-diol metabolites, with or without stimulation with phorbol myristate acetate (PMA). DNA adducts of B[a]P-metabolites were determined in target cells using 32P-postlabeling; oxidative DNA damage (7-hydro-8-oxo-2'-deoxyguanosine [8-oxodG]) was evaluated by high performance liquid chromatography with electrochemical detection. Increased DNA adducts were observed in lung cells coincubated with polymorphonuclear leukocytes (PMN). Activation of PMN with PMA, or addition of more activated PMN in relation to the number of lung cells, further increased the number of adducts, the latter in a dose-response manner. Incubation with B[a]P-4,5-diol did not result in any adduct formation, while B[a]P-7,8-diol led to a significant number of adducts. Moreover, PMA-activated PMN strongly enhanced adduct formation by B[a]P-7,8-diol, but not 8-oxodG, in lung cells. The addition of antioxidants to the coincubations significantly reduced the number of adducts. Results suggest that an inflammatory response in the lung may increase the biologically effective dose of polycyclic aromatic hydrocarbons (PAHs), and may be relevant to data interpretation and risk assessment of PAH-containing particulates.

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Section: Discussionsupporting

confidence: 92%

Neutrophils Amplify the Formation of DNA Adducts by Benzo[a]pyrene in Lung Target Cells

Borm¹,

Knaapen²,

Schins³

et al. 1997

Environmental Health Perspectives

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show abstract

“…Parallel analysis of oxidative DNA damage showed that stimulation by phorbol ester caused enhanced ratios of 8-oxodG/dG in PMN, which is in agreement with previous observations (18,23) but in contrast to a recent study (24). In …”

Section: Dna Isolationsupporting

confidence: 91%

Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.

Borm

Knaapen

Schins

et al. 1997

Environ Health Perspect

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“…Recent evidence also implicates HNE in various key signaling processes [46, 47]. 8-hydroxy-2′-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) is a marker of free radical-induced oxidative damage in nuclear and mitochondrial DNA, which has been widely used as a biomarker for oxidative stress and carcinogenesis [48–53]. Nitrotyrosine (3-NT) formation was initially considered a specific marker of in vivo peroxynitrite generation, but now it is rather used as a collective index of protein nitration, because other pathways have also been proposed to be involved in its formation (e.g., myeloperoxidase under certain inflammatory conditions [21, 54–58].…”

Section: Resultsmentioning

confidence: 99%

Poly(ADP-ribose) polymerase-1 is a key mediator of cisplatin-induced kidney inflammation and injury

Mukhopadhyay

Horváth

Kechrid

et al. 2011

Free Radical Biology and Medicine

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Cisplatin is a commonly used chemotherapeutic drug the clinical use of which is limited by the development of dose-dependent nephrotoxicity. Enhanced inflammatory response, oxidative stress and cell death have been implicated in the development of cisplatin-induced nephropathy; however the precise mechanisms are elusive. Overactivation of the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1) by oxidative DNA damage in various pathological conditions promotes cell death and up-regulation of key proinflammatory pathways. In this study, using a well-established model of nephropathy, we have explored the role of PARP-1 in cisplatin-induced kidney injury. Genetic deletion or pharmacological inhibition of PARP-1 markedly attenuated the cisplatin-induced histopathological damage, impaired renal function (elevated serum BUN and creatinine levels), enhanced inflammatory response (leukocyte infiltration, TNF-α, IL-1β, F4/80, adhesion molecules ICAM-1/VCAM-1 expressions) and consequent oxidative/nitrative stress (HNE, 8-OHdG, and nitrotyrosine content, NOX2/NOX4 expressions). PARP inhibition also facilitated the cisplatin-induced cell death in cancer cells. Thus, PARP activation plays an important role in cisplatin-induced kidney injury, and its pharmacological inhibition may represent a promising approach to prevent the cisplatin-induced nephropathy. This is particularly exciting since several PARP inhibitors alone or in combination with DNA-damaging anticancer agents show considerable promise in clinical trials to treat various malignancies (e.g. triple-negative breast cancer).

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8-Hydroxydeoxyguanosine in DNA from TPA-Stimulated Human Granulocytes

Cited by 6 publications

References 29 publications

Neutrophils Amplify the Formation of DNA Adducts by Benzo[a]pyrene in Lung Target Cells

Neutrophils Amplify the Formation of DNA Adducts by Benzo[a]pyrene in Lung Target Cells

Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.

Poly(ADP-ribose) polymerase-1 is a key mediator of cisplatin-induced kidney inflammation and injury

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