Enhanced levels of DNA adducts in the liver of woodchucks infected with hepatitis virus

Izzotti, Alberto; Scatolini, L; Lewtas, Joellen; Walsh, Debra; Flora, Silvio De

doi:10.1016/0009-2797(95)03622-s

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…Moreover, GSH stores appear to be depleted in chronic infections caused by at least three viruses (e.g., hepatitis B virus [HBV], hepatitis C virus [HCV;], and human immunodeficiency virus [HIV]) typically associated with cancer. In fact, both humans infected with HBV and woodchucks infected with woodchuck hepatitis virus display enhanced metabolic activation of chemical hepatocarcinogens, accompanied in woodchucks by GSH depletion related to the amounts of virus in hepatocytes (22)(23)(24). GSH levels decreased in both plasma and peripheral-blood lymphocytes of patients De Flora et al…”

Section: Nac and The Glutathione Systemmentioning

confidence: 99%

Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

Flora¹,

Izzotti²,

Albini³

et al. 2004

Cancer Chemoprevention

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Section: Nac and The Glutathione Systemmentioning

confidence: 99%

Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

Flora¹,

Izzotti²,

Albini³

et al. 2004

Cancer Chemoprevention

Self Cite

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“…A synergism has been also demonstrated between alcohol drinking and infection with either HBV or HCV (54). There is an enhanced metabolic activation of chemical hepatocarcinogens, and especially of heterocyclic amines, both in HBV-infected hepatocytes (56) and in woodchuck hepatitis virus-infected hepatocytes (57)(58)(59). These foodderived mutagens induce cancer in the liver and other organs when given to rodents in the diet (60).…”

Section: Hbv-associated Hccmentioning

confidence: 99%

The prevention of infection-associated cancers

Flora

Bonanni

2011

Carcinogenesis

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Collectively, chronic viral and bacterial infections and trematode infestations have been estimated to be associated with approximately one of five human cancers worldwide. The fraction attributable to each one of the chronic infections caused by hepatitis B and C viruses (HBV and HCV), human papillomaviruses (HPV) and Helicobacter pylori, is ∼5%. These infections are the most important causes of major types of cancer, including hepatocellular carcinoma, cervical cancer and stomach cancer, respectively. Taking into account the mechanisms of infection-related carcinogenesis, integrated approaches are addressed to the control of the associated infection as well as to avoidance of cancer occurrence and progression. Large-scale interventions have been implemented, such as the anti-HBV and anti-HPV routine vaccination programs. The latter has been designed with the specific goal of preventing HPV-associated cancers, which is an outstanding breakthrough in cancer prevention. Intriguingly, not only prevention but even therapy of an infectious disease and eradication of a pathogen become a crucial tool for the primary prevention of these cancers. An important role is also played by secondary prevention (e.g. Pap test and DNA testing for HPV-associated cervical cancers) and by tertiary prevention (e.g. antiangiogenesis in Kaposi's sarcoma). The present article reviews the microbial and parasitic diseases that have been associated so far with human cancers, draws an overview of their burden in cancer epidemiology, deals with applicable prevention strategies and provides examples of co-ordinated approaches to the control of cancers associated with HBV, HCV, HPV, human immunodeficiency virus and H.pylori infections.

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“…In a transgenic mouse model LHBs transactivator expression had already been shown to induce 8-OHdG adducts [30, 40]. Also the woodchuck hepatitis virus surface protein or entire virions have been reported to increase NO radical production [41]and 8-OHdG adduct formation within genomic DNA [42]. For our experiments, we used a well-validated technique for the extraction of genomic DNA to exclude oxidation of DNA during DNA extraction [37, 38].…”

Section: Discussionmentioning

confidence: 99%

Accumulation of 8-Hydroxy-2’- Deoxyguanosine Adducts in HBx Recombinant HepG2 Cells and HBx Transgenic Mice

et al. 2004

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Background/Aims: Transgenic mice overexpressing hepatitis B x protein (HBx) show an increased susceptibility to mutations if exposed to mutagens. Also involved in HBx signalling, reactive oxygen intermediates (ROI) can induce DNA adducts such as 8-hydroxy-2′-deoxyguanosine that can in turn lead to G/T transversion mutations. Therefore, we investigated whether HBx expression increases the level of the mutational precursor 8-hydroxy-2′-deoxyguanosine in hepatocellular DNA. Methods: 8-hydroxy-2′-deoxyguanosine concentrations of DNA hydrolysates of HBx protein expressing HepG2 cells and livers of HBx transgenic mouse lines were determined electrochemically after HPLC fractionation. Results: 8-hydroxy-2′-deoxyguanosine concentrations in genomic DNA of HBx protein expressing cell lines correlated with the factor of transactivation. The 8-hydroxy-2′-deoxyguanosine levels were reduced after incubation of HBx recombinant cell lines with 0.1 or 1 mM of the antioxidant N-acetylcysteine. Hepatic 8-hydroxy-2′-deoxyguanosine concentrations in DNA of old transgenic mice were significantly, i.e. twofold, (p < 0.01) increased as compared to those of old nontransgenic or young transgenic controls and of control mice expressing a second HBV transactivator (MHBs^t76). Conclusion: HBx expression results in elevated DNA adduct levels. This could reflect a direct inhibitory interaction of HBx with cellular repair mechanisms. Alternatively, this may be an effect of an increased generation of reactive oxygen intermediates through HBx.

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Enhanced levels of DNA adducts in the liver of woodchucks infected with hepatitis virus

Cited by 7 publications

References 24 publications

Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

Antigenotoxic and Cancer Preventive Mechanisms of N-Acetyl-l-Cysteine

The prevention of infection-associated cancers

Accumulation of 8-Hydroxy-2’- Deoxyguanosine Adducts in HBx Recombinant HepG2 Cells and HBx Transgenic Mice

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