In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase

Espina, Noel; Lima, Viera; Lieber, Charles S.; Garro, Anthony J.

doi:10.1093/carcin/9.5.761

Cited by 149 publications

(55 citation statements)

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“…1B, 4D and E, and 6A and E). In particular, acetaldehyde, which inhibits cell proliferation (47), is a carcinogen in rats (48) and humans (49) and inhibits DNA repair enzymes (50). H 2 O 2 is a common form of reactive oxygen species (ROS) that damages cell membranes via lipid oxidation (51).…”

Section: Discussionmentioning

confidence: 99%

Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

et al. 2015

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Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (⌬adhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H 2 O 2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ⌬adhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ⌬adhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence.

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Section: Discussionmentioning

confidence: 99%

Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

et al. 2015

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“…In our study, Val 143 was associated with reduced head and neck cancer risk, particularly among heavy drinkers. In vivo and in vitro experiments show that MGMT-mediated repair of alkylated DNA is reduced by treatment with ethanol or its primary metabolite, acetaldehyde (42,43), possibly due to MGMT inhibition (44). Although the functional importance of either the MGMT codon 84 or 143 variants is unknown (25,28), both are evolutionarily conserved (26,27) and the MGMT 143 polymorphism is close to the Cys 145 alkyl acceptor site (26).…”

Section: Discussionmentioning

confidence: 99%

Selected Genetic Polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and Risk of Head and Neck Cancer: A Pooled Analysis

Huang

Olshan

Schwartz

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

109

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Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites

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“…Acetaldehyde directly inhibits O 6 -methylguanosyl transferase, an enzyme important for the repair of DNA adducts (Espina et al, 1988). In the liver, acetaldehyde forms adducts with intracellular proteins and DNA, resulting in morphological and functional impairment of the cell, and a humoral immune reaction towards de novo generated antigens.…”

Section: Acetaldehydementioning

confidence: 99%

“…This is due to acetaldehyde-related inhibition of O 6 -guanine-methyl transferase (Espina et al, 1988) (Figure 3). …”

Section: Alteration Of the Antioxidative Defense System And Inhibitiomentioning

confidence: 99%

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

Seitz

Stickel

2006

Biological Chemistry

274

178

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Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in women worldwide. Established risk factors are chronic hepatitis B and C infection, chronic heavy alcohol consumption, obesity and type 2 diabetes, tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost 90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western countries, attributable risks are highest for cirrhosis due to chronic alcohol abuse and viral hepatitis B and C infection. Among those with alcoholic cirrhosis, the annual incidence of hepatocellular cancer is 1-2%. An important mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress from alcohol metabolism, inflammation, and increased iron storage. Ethanolinduced cytochrome P-450 2E1 produces various reactive oxygen species, leading to the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol impairs the antioxidant defense system, resulting in mitochondrial damage and apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to the activation of survival factors and interference with retinoid metabolism. Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and may thereby alter gene expression.

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In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O⁶-methylguanine transferase

Cited by 149 publications

References 0 publications

Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

Ethanol-Induced Alcohol Dehydrogenase E (AdhE) Potentiates Pneumolysin in Streptococcus pneumoniae

Selected Genetic Polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and Risk of Head and Neck Cancer: A Pooled Analysis

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

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