Etheno adducts formed in DNA of vinyl chloride-exposed rats are highly persistent in liver

Swenberg, James A.; Fedtke, N.; Ciroussel, Françoise; Barbin, Alain; Bartsch, Helmut

doi:10.1093/carcin/13.4.727

Cited by 114 publications

(75 citation statements)

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“…[36][37][38] Excess levels of etheno-adducts have been detected in chronically inflamed or infected organs of cancer-prone patients. 39 Exocyclic nucleobase adducts exhibit pro-mutagenic properties 8,40 and apparently are poorly repaired in some tissues and cells, 41,42 indicating that they may be of considerable biological importance. Etheno-DNA adducts probably play a causal role in the initiation and progression of liver carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Ethanol‐induced cytochrome P4502E1 causes carcinogenic etheno‐DNA lesions in alcoholic liver disease†‡

et al. 2009

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Oxidative stress is thought to play a major role in the pathogenesis of hepatocellular cancer (HCC), a frequent complication of alcoholic liver disease (ALD). However, the underlying mechanisms are poorly understood. In hepatocytes of ALD patients, we recently detected by immunohistochemistry significantly increased levels of carcinogenic etheno-DNA adducts that are formed by the reaction of the major lipid peroxidation product, 4-hydroxynonenal (4-HNE) with nucleobases. In the current study, we show that protein-bound 4-HNE and etheno-DNA adducts both strongly correlate with cytochrome P450 2E1 (CYP2E1) expression in patients with ALD (r ‫؍‬ 0.9, P < 0.01). Increased levels of etheno-DNA adducts were also detected in the liver of alcohol-fed lean ( E xcess consumption of alcohol is widespread inWestern countries and, in the United States, alcohol abuse affects approximately 18 million adults. 1 The consumption of more than 80 g ethanol per day for more than 10 years increases the risk for hepatocellular carcinoma (HCC) by approximately fivefold. 2 Worldwide, HCC is one of the most common malignant tumors, ranking as the seventh most prevalent in men and the ninth in women. The risk for HCC in decompensated alcohol-induced cirrhosis is approximately 1% to 2% per year. 2 Although the evolution of alcohol-related HCC involves several factors, 3,4 including the presence of cirrhosis, oxidative stress, disturbed DNA methylation, and defective retinoic acid signaling, the precise mechanisms at a molecular level by which alcohol causes HCC are poorly understood. Recently, the International Agency for Research on Cancer has classified ethanol as a human (group 1) carcinogen, because it induces HCC (among other tumors) in animals and increases the risk for developing HCC in humans. 3,5,6

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Section: Discussionmentioning

confidence: 99%

Ethanol‐induced cytochrome P4502E1 causes carcinogenic etheno‐DNA lesions in alcoholic liver disease†‡

et al. 2009

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“…7-(2'-Oxoethyl)guanine and three etheno adducts (-A; £C; and N2,3-EG; Figure 2) have been detected in DNA from rats and mice exposed to VC (123,(128)(129)(130)(131). Highly variable background levels ofcA and -C were found in all the tissues examined (132,133).…”

Section: Vc Initiation Of Hepatocarcinogenesismentioning

confidence: 95%

Vinyl Chloride: Still a Cause for Concern

Kielhorn¹,

Melber²,

Wahnschaffe³

et al. 2000

Environmental Health Perspectives

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“…In addition to abasic sites, exocyclic DNA adducts, such as ethano-bases are strong topoisomerase II poisons [177,179]. These adducts are generated following peroxidation of cellular lipids or by exposure of cells to industrial chemicals such as vinyl chloride [183,184].…”

Section: Dna Lesions As Topoisomerase II Poisonsmentioning

confidence: 99%

DNA topoisomerase II, genotoxicity, and cancer

McClendon

Osheroff

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

363

466

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Type II topoisomerases are ubiquitous enzymes that play essential roles in a number of fundamental DNA processes. They regulate DNA under-and overwinding, and resolve knots and tangles in the genetic material by passing an intact double helix through a transient double-stranded break that they generate in a separate segment of DNA. Because type II topoisomerases generate DNA strand breaks as a requisite intermediate in their catalytic cycle, they have the potential to fragment the genome every time they function. Thus, while these enzymes are essential to the survival of proliferating cells, they also have significant genotoxic effects. This latter aspect of type II topoisomerase has been exploited for the development of several classes of anticancer drugs that are widely employed for the clinical treatment of human malignancies. However, considerable evidence indicates that these enzymes also trigger specific leukemic chromosomal translocations. In light of the impact, both positive and negative, of type II topoisomerases on human cells, it is important to understand how these enzymes function and how their actions can destablize the genome. This article discusses both aspects of human type II topoisomerases.

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Etheno adducts formed in DNA of vinyl chloride-exposed rats are highly persistent in liver

Cited by 114 publications

References 0 publications

Ethanol‐induced cytochrome P4502E1 causes carcinogenic etheno‐DNA lesions in alcoholic liver disease†‡

Ethanol‐induced cytochrome P4502E1 causes carcinogenic etheno‐DNA lesions in alcoholic liver disease†‡

Vinyl Chloride: Still a Cause for Concern

DNA topoisomerase II, genotoxicity, and cancer

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