Increased Oxidative Damage to Mitochondrial DNA Following Chronic Ethanol Consumption

Cahill, Alan; Wang, Xiaolan; Hoek, Jan B.

doi:10.1006/bbrc.1997.6774

Cited by 110 publications

(77 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cigarette smoking is a life-style factor that has adverse effects on sperm, and it also leads to increases in sperm 8-OHdG (222,223). Alcohol consumption has been associated with sperm damage, and we have evidence that alcohol consumption leads to increased oxidative stress in many tissues, including the formation of 8-OHdG in hepatic mitochondrial DNA of rats (224). However, an association between alcohol consumption and oxidative damage in sperm has not been reported in the literature.…”

Section: Oxidative Stress and Dna Damage In Spermmentioning

confidence: 83%

Understanding the human health effects of chemical mixtures.

Carpenter

Arcaro

Spink

2002

Environ Health Perspect

329

198

View full text Add to dashboard Cite

Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.

show abstract

Section: Oxidative Stress and Dna Damage In Spermmentioning

confidence: 83%

Understanding the human health effects of chemical mixtures.

Carpenter

Arcaro

Spink

2002

Environ Health Perspect

329

198

View full text Add to dashboard Cite

show abstract

“…It was shown a significant higher risk for cancer of the hypopharynx than for larynx cancer with alcohol drinking, which may be explained by the fact that hypopharynx enters in contact with the bolus (alcohol) and the air (tobacco smoke) while air pass through larynx but not the bolus (Esteve et al, 1996;Menvielle et al, 2004). Alcohol is known to cause oxidative stress through production of ROS (Hoek et al, 2002) and ethanol consumption has been reported to induce oxidative damage to mtDNA with increased levels of 8-hydroxydeoxyguanosin in rats (Cahill et al, 1997). The abasic sites and oxidised bases generated could so be responsible for mtDNA mutations.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma

et al. 2006

View full text Add to dashboard Cite

Mitochondrial DNA mutations have been reported in several types of tumours, including head and neck squamous cell carcinoma (HNSCC). The noncoding region of the Displacement-Loop (D-Loop) has emerged as a mutational hotspot and we recently found that they were associated with prognosis and response to 5 fluorouracil (5FU) in colon cancers. In order to evaluate the frequence of D-Loop mutations in a large series of HNSCC and establish correlations with clinicopathologic parameters, we sequenced the D-Loop of 109 HNSCC before a treatment by neoadjuvant 5FU-cisplatin-based chemotherapy and surgery. Then, we correlated these mutations with prognosis and response to chemotherapy. A D-Loop mutation was identified in 21% of the tumors, the majority of them were located in a C-tract (D310). The prevalence of D310 mutations increased significantly with the number of cytosines in the matched normal tissue sequence (P ¼ 0.02). Hypopharyngeal cancer was significantly more frequent (P ¼ 0.03) and tobacco consumption more important (P ¼ 0.01) in the group of patients with D-Loop mutation. The presence of D-Loop mutation was not associated with prognosis or with response to neoadjuvant chemotherapy. These results suggest that D-Loop mutations should be considered as a cancer biomarker that may be useful for the early detection of HNSCC in individuals at risk of this cancer.

show abstract

“…Moreover, this decrease in ADP-stimulated respiration is linked to decreased electron transport in all segments of the respiratory chain as chronic alcohol consumption decreases the activities of all the respiratory complexes, except complex II [41,42]. Several laboratories have presented strong evidence that inhibition of mitochondrial protein synthesis [43] linked to mtDNA damage [44][45][46] and ribosomal defects [47,48] contribute, in part, to decreased functioning of the oxidative phosphorylation system following chronic alcohol consumption. These alterations translate into profound modifications to the mitochondrial proteome that encompass not only losses in the 13 mitochondrial encoded polypeptides, but also decreases in numerous nuclear encoded proteins that make up the oxidative phosphorylation complexes [46].…”

Section: Mitochondria Dysfunction In Fatty Liver Diseases -Bioenergetmentioning

confidence: 99%

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Mantena

King

Andringa

et al. 2008

Free Radical Biology and Medicine

388

302

View full text Add to dashboard Cite

Fatty liver disease associated with chronic alcohol consumption or obesity/type 2 diabetes has emerged as a serious public health problem. Steatosis, accumulation of triglyceride in hepatocytes, is now recognized as a critical "first-hit" in the pathogenesis of liver disease. It is proposed that steatosis "primes" the liver to progress to more severe liver pathologies when individuals are exposed to subsequent metabolic and/or environmental stressors or "second-hits". Genetic risk factors can also influence the susceptibility and severity of fatty liver disease. Furthermore, oxidative stress, disrupted nitric oxide (NO) signaling, and mitochondrial dysfunctional are proposed to be key molecular events that accelerate or worsen steatosis and initiate progression to steatohepatitis and fibrosis. This review article will discuss the following topics regarding the pathobiology and molecular mechanisms responsible for fatty liver disease: 1) the "two-hit" or "multi-hit" hypothesis; 2) the role of mitochondrial bioenergetic defects and oxidant stress; 3) interplay between NO and mitochondria in fatty liver disease; 4) genetic risk factors and oxidative stress responsive genes; and 5) the feasibility of antioxidants for treatment.

show abstract

Increased Oxidative Damage to Mitochondrial DNA Following Chronic Ethanol Consumption

Cited by 110 publications

References 32 publications

Understanding the human health effects of chemical mixtures.

Understanding the human health effects of chemical mixtures.

Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma

Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases

Contact Info

Product

Resources

About