Mutagenesis and carcinogenesis: Endogenous and exogenous factors

Ames, Bruce N.

doi:10.1002/em.2850140614

Cited by 241 publications

(89 citation statements)

References 87 publications

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“…During the initiation phase of this process, ROS may interact directly with DNA, damaging specific genes that control cell growth and differentiation, among others [36]. They can also increase the activity of carcinogenic xenobiotics by facilitating their activation to reactive compounds [37]. During the progression phase of carcinogenesis, ROS can directly stimulate the growth of cancer cells [38].…”

Section: Hepatocellular Carcinoma and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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Section: Hepatocellular Carcinoma and Free Radicalsmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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“…It is plausible that ROS released by inflammatory cells during cycles of cellular damage and regeneration in the organ result in permanent DNA damage (55). The prostate gland is a common site of chronic inflammation.…”

Section: Mol Cancer Res 2008;6(2) February 2008mentioning

confidence: 99%

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Uemura

Ishiguro

et al. 2008

Molecular Cancer Research

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Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2 ¶-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O 2 À ) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2 ¶-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O 2 À radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed. (Mol Cancer Res 2008;6(2):250 -8)

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“…Microbial elicitors of host-resistance responses include peptides and enzymes, fatty acids, polysaccharides, and glycoproteins. Elicitors (inducers) appear to be both exogenous and endogenous (6) (20 of 42) were found to be carcinogenic (7).…”

Section: Phytoalexinsmentioning

confidence: 99%

Cellular Responses to Oxidative Stress: The [Ah] Gene Battery As a Paradigm

Nebert¹,

Petersen²,

Fornace³

1990

Environmental Health Perspectives

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A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYPIAI and CYPIA2; and four Phase II genes, Nmo-1, Aldh-i, Ugt-1, and Gt-l. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-l gene expression is independent of the control of CYPIAI and CYPIA2 gene expression. The radiation deletion homozygote c 4Cot/C14Co5mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYPIAI or CYPIA2 activation, the untreated C14CI/C14Cos mouse exhibits markedly elevated transcripts of the Nmo-i gene and three growth arrest-and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the C14CoS/C14CoS mouse contains a gene(s), which we propose to call Nmo-In, encoding a trans-acting factor(s) that is a negative effector of the Nmo-l and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the C14CoS/C14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria.

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Mutagenesis and carcinogenesis: Endogenous and exogenous factors

Cited by 241 publications

References 87 publications

Role of free radicals in liver diseases

Role of free radicals in liver diseases

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Cellular Responses to Oxidative Stress: The [Ah] Gene Battery As a Paradigm

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