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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of cancer is in many way different than in healthy cells. Increased metabolism of several carcinogenic substances may take place in cancer cells. The one of them was ethanol, that is oxidized by alcohol dehydrogenase (ADH) to high concentration of acetaldehyde, a toxic and carcinogenic compound. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). The aim of this study was to compare the capacity for ethanol metabolism measured by ADH isoenzymes and ALDH activity between gastric cancer and normal gastric mucosa. Total ADH activity was measured by photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I isoenzymes, we used fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as a substrate. The samples were taken surgically during routine operations of gastric carcinomas from 55 patients. The activities of total ADH, and the most important in gastric mucosa, class IV ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH and ALDH showed a tendency toward higher activity in cancer than in healthy mucosa. The activities of all tested enzymes and isoenzymes were not significantly higher in men than in women in wither gastric cancer tissues or normal mucosa. The increased ADH IV activity may be 1 of the factors intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol.
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PMID:The activity of class I, III, and IV of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in gastric cancer. 1721 7

N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2'-deoxyguanosine (N2-Et-dG) and alpha-methyl-gamma-hydroxy-1,N2-propano-2'-deoxyguanosine (alpha-Me-gamma-OH-PdG) in the liver DNA of aldehyde dehydrogenase (Aldh)-2-knockout mice to determine the influence of alcohol consumption and the Aldh2 genotype on the levels of DNA damage. In control Aldh2+/+ mice, the level of N2-ethylidene-dG adduct in liver DNA was 1.9 +/- 0.7 adducts per 10(7) bases and was not significantly different than that of Aldh2+/- and -/- mice. In alcohol-fed mice (20% ethanol for 5 weeks), the adduct levels of Aldh2+/+, +/- and -/- mice were 7.9 +/- 1.8, 23.3 +/- 4.0 and 79.9 +/- 14.2 adducts per 10(7) bases, respectively, and indicated that adduct level was alcohol and Aldh2 genotype dependent. In contrast, an alcohol- or Aldh2 genotype-dependent increase was not observed for alpha-Me-gamma-OH-PdG, and N2-Et-dG was not detected in any of the analyzed samples. In conclusion, the risk of formation of N2-ethylidene-dG in model animal liver in vivo is significantly higher in the Aldh2-deficient population and these results may contribute to our understanding of in vivo adduct formation in humans.
Carcinogenesis 2007 Nov
PMID:Increased formation of hepatic N2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol. 1736 Oct 10

Chronic excessive alcohol consumption is the strongest risk factor for upper aerodigestive tract (UADT) cancer. Multiple mechanisms are involved in alcohol-associated cancer development of the UADT, including acetaldehyde (AA) effects. AA is toxic, mutagenic, and carcinogenic. Evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphism or mutation in genes coding for AA generation or detoxification enzymes are associated with increased cancer risk. It has been clearly shown in Asians that individuals carrying the acetaldehyde dehydrogenase 2*2 (ALDH2*2) allele have a significantly increased cancer risk when they consume alcohol. In Caucasians, alcohol dehydrogenase 1*1 (ADH1C*1) allele encodes for an alcohol dehydrogenase (ADH) isoenzyme, which produces 2.5 times more AA than the corresponding allele ADH1C*2. The authors found that the ADH1C*1 allele frequency and rate of homozygosity was significantly associated with an increased risk for alcohol-related cancer. AA seems to be an important factor in alcohol-associated carcinogenesis of the UADT.
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PMID:The role of acetaldehyde in upper digestive tract cancer in alcoholics. 1754 46

Acetaldehyde has been classified as a carcinogen in experimental animal research. Acetaldehyde is highly toxic, mutagenic and carcinogenic. Acetaldehyde causes point mutations, sister chromatid exchanges and gross chromosomal aberrations. In the liver, acetaldehyde binds to DNA and the formation of stable adducts represents one mechanism by which acetaldehyde could trigger the occurrence of replication errors and/or mutations in oncogenes or tumour suppressor genes. In experimental colorectal carcinogenesis the inhibition of acetaldehyde dehydrogenase with elevated acetaldehyde levels results in an acceleration of cancer development. The production of acetaldehyde is reduced when germ-free animals are studied, emphasizing the role of bacteria in the generation of colorectal acetaldehyde. Acetaldehyde levels in the colorectum correlate with crypt cell production rate and result in hyper-regeneration, a precancerous condition. Genetic linkage studies give further evidence for acetaldehyde as a carcinogen. Individuals who accumulate acetaldehyde due to polymorphism and/or mutations in the genes coding for enzymes responsible for acetaldehyde generation and detoxification have an increased cancer risk. This is true for Asians with low acetaldehyde dehydrogenase 2 and for Caucasians with alcohol dehydrogenase 1C*1/1. In conclusion, there is an enormous body of evidence from in vitro studies, animal experiments and genetic linkage studies, that acetaldehyde is the major factor responsible for tumour development in alcohol-associated carcinogenesis of the gastrointestinal tract.
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PMID:The role of acetaldehyde in alcohol-associated cancer of the gastrointestinal tract. 1759 Sep 90

Approximately 3.6% of cancers worldwide derive from chronic alcohol drinking, including those of the upper aerodigestive tract, the liver, the colorectum and the breast. Although the mechanisms for alcohol-associated carcinogenesis are not completely understood, most recent research has focused on acetaldehyde, the first and most toxic ethanol metabolite, as a cancer-causing agent. Ethanol may also stimulate carcinogenesis by inhibiting DNA methylation and by interacting with retinoid metabolism. Alcohol-related carcinogenesis may interact with other factors such as smoking, diet and comorbidities, and depends on genetic susceptibility.
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PMID:Molecular mechanisms of alcohol-mediated carcinogenesis. 1764 65

Chronic alcohol consumption is a major risk factor for upper aero-digestive tract cancers, including cancer of the esophagus. Whereas alcohol as such is not thought to be directly carcinogenic, acetaldehyde, its first metabolite, has been proven genotoxic and mutagenic in the HPRT gene. As mutations in the tumour suppressor gene TP53 are the most common genetic alterations involved in human cancers, especially esophageal tumours, the aim of this work was to establish the mutational pattern induced by acetaldehyde in vitro on the TP53 gene, and to compare this pattern with that found in human alcohol-related tumours. For this purpose, we used a functional assay in yeast, the FASAY (functional analysis of separated alleles in yeast), after in vitro exposure of human normal fibroblasts AG1521 to acetaldehyde. We noted 35 mutations, of which 32 were single-nucleotide substitutions including 2 nonsense and 30 missense mutations. The pattern showed that the main mutations were G>A transitions (n=23, of which 14 in CpG sites), followed by G>T transversions (n=4), A>G transitions (n=2) and A>T transversions (n=2). Other mutations were one-base insertion and two deletions, leading to frameshifts. Eleven mutations (31%) were located in TP53 hot-spots in codons 245, 248, 249 and 273. Finally, we compared this pattern with that found for esophageal cancers in humans. These results support the notion that acetaldehyde plays a role in TP53 mutations in esophageal cancers. The key feature of this approach is that mutagenesis is directly studied in a key gene in human carcinogenesis, allowing direct comparison of mutational patterns with those in human tumours.
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PMID:Acetaldehyde-induced mutational pattern in the tumour suppressor gene TP53 analysed by use of a functional assay, the FASAY (functional analysis of separated alleles in yeast). 1824 17

Epidemiological data have identified chronic alcohol consumption as a significant risk factor for cancer in humans. The exact mechanism of ethanol-associated carcinogenesis has remained unknown. The metabolism of ethanol leads to generation of acetaldehyde (AA), which is highly toxic and carcinogenic. The amount of acetaldehyde to which cells or tissues are exposed after alcohol ingestion may be of great importance and may, among others, affects carcinogenesis. Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH). The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase (ALDH). Both formation and degradation of acetaldehyde depends on the activity of these enzymes. The total alcohol dehydrogenase activity is significantly higher in cancer tissues than in this healthy organs (e.g. liver, stomach, esophagus, colorectum). Moreover the activity of ADH is much higher than the activity of ALDH. This suggests that cancer cells have a greater capability for ethanol oxidation but less ability to remove acetaldehyde than normal tissues. In addition significant differences of ADH isoenzymes activities between cancer tissues and healthy organs may be a factor intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol and disorders in metabolism of some biologically important substances (e.g. retinoic acid). The changes in activity of particular ADH isoenzymes in the sera of patients with different cancers, seem to be caused by release of these isoenzymes from cancer cells, and may be useful for diagnostics of this cancer. The particular isoenzymes of ADH present in the serum may indicate the cancer localization.
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PMID:Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases. 1850 83

Chronic alcohol consumption is a risk factor for many cancers, e.g. upper digestive tract, liver, pancreas, colorectum and breast. The main role in carcinogenesis plays toxic and carcinogenic acetaldehyde. Formation and degradation of acetaldehyde in the body is modified by activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). They are polymorphic enzymes localized in different organs and catalyzing many others biochemical reactions.
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PMID:[Alcohol dehydrogenase and aldehyde dehydrogenase in malignant diseases--part I]. 1870 45

We present a novel concept on carcinogenesis mediated by oral microbiota. Oral micro-organisms are capable of metabolizing alcohol to acetaldehyde. This finding casts light on the observed association between poor oral hygiene and oral cancer. Ethanol, as such, is not carcinogenic, but its first metabolite acetaldehyde is indisputably carcinogenic. Several gastro-intestinal microbial species possess the enzyme alcohol dehydrogenase (ADH), which is also the enzyme responsible for alcohol metabolism in the liver. In oral microbiota, we observed that species such as the ubiquitous viridans streptococci and Candida also possess ADH. Ethanol can be detected in the mouth hours after the consumption of alcoholic beverages. Patients with poor oral health status have shown higher salivary acetaldehyde concentrations than those with better oral health. It is thus understandable that ADH-containing micro-organisms in the mouth present a risk for carcinogenic acetaldehyde production, with subsequent potential for the development of oral cancer, particularly among heavy drinkers. In this article, we briefly review this area of investigation and conclude by highlighting some future possibilities for the control of carcinogenesis.
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PMID:Oral micro-organisms in the etiology of cancer. 1882 Oct 87

Heavy alcohol consumption is associated with increased risk of cancers including digestive tract, liver, pancreas, colorectum and breast. Direct correlations between alcohol consumption and development of cancer are still unknown. The differences in activities of ADH and ALDH between cancer tissues and normal mucosa might be a factor for metabolic changes and disturbances in low- mature cancer cells, might be a reason for the high level of acetaldehyde and intensifying carcinogenesis. Moreover releasing ADH and ALDH from cancer cells can cause increase of these enzymes activities in the sera of patients with cancer.
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PMID:[Alcohol dehydrogenase and aldehyde dehydrogenase in malignant diseases--Part II]. 1894 44


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