Alcohol Abuse: Carcinogenic Effects and Fetal Alcohol Syndrome

Garro, Anthony J.; Gordon, Barbara H. J.; Lieber, Charles S.

doi:10.1007/978-1-4615-3320-7_15

Cited by 11 publications

(7 citation statements)

References 284 publications

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“…Two epidemiologic investigations, namely the ATBC 49 and the CARET 50 studies, revealed that β‐carotene supplementation increases the incidence of pulmonary cancer in smokers. Because heavy smokers are commonly heavy drinkers, we raised the possibility that alcohol abuse was contributory, 51 since alcohol is known to act as a carcinogen and to exacerbate the carcinogenicity of other xenobiotics, especially those of tobacco smoke 52 . The more recent publications of the ATBC and CARET studies showed that the increased incidence of pulmonary cancer was indeed related to the amount of alcohol consumed by the participants 53,54 …”

Section: Pathogenesis and Related Therapymentioning

confidence: 99%

Liver Diseases by Alcohol and Hepatitis C: Early Detection and New Insights in Pathogenesis Lead to Improved Treatment

Lieber

2001

American J Addict

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Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of treatment. Therapy must include correction of nutritional deficiencies, while taking into account changes of nutritional requirements. Methionine is normally activated to S-adenosylmethionine (SAMe). However, in liver disease, the corresponding enzyme is depressed. The resulting deficiencies can be attenuated by the administration of SAMe but not by methionine. Similarly, phosphatidylethanolamine methyltransferase activity is depressed, but the lacking phosphatidylcholine (PC) can be administrated as polyenylphosphatidylcholine (PPC). Chronic ethanol consumption increases CYP2E1, resulting in increased generation of toxic acetaldehyde and free radicals, tolerance to ethanol and other drugs, and multiple ethanol-drug interactions. Experimentally, PPC opposes CYP2E1 induction and fibrosis. Alcoholism and hepatitis C infection commonly co-exist, with acceleration of fibrosis, cirrhosis, and hepatocellular carcinoma. PPC is being tested clinically as a corresponding antifibrotic agent. Available antiviral agents are contraindicated in the alcoholic. Anti-inflammatory agents, such as steroids, may be selectively useful. Finally, anticraving agents, such as naltrexone or acamprosate, should be part of therapy.

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Section: Pathogenesis and Related Therapymentioning

confidence: 99%

Liver Diseases by Alcohol and Hepatitis C: Early Detection and New Insights in Pathogenesis Lead to Improved Treatment

Lieber

2001

American J Addict

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“…The in situ formation of acetaldehyde and the increased susceptibility to oxidative stress exhibited by the rat ovarian tissue here described might play a role in these deleterious effects observed. In effect, acetaldehyde is a well-known mutagenic chemical that is known to attack DNA, proteins, lipids and other cellular components (Dellarco, 1998;Garro et al, 1992). Similarly, it was repetitively shown by many workers in the field that oxidative stress is a highly deleterious process provoking generalized derangement of almost every cellular component through its effects on DNA, proteins and other cell molecules (Lu and Cederbaum, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The generation of acetaldehyde in situ may harm ovarian tissue. In effect, it is well known that acetaldehyde is a mutagenic, carcinogenic and toxic chemical able to react with DNA, proteins and lipids and with many other relevant molecules such as GSH (Dellarco, 1998;Garro et al, 1992). Those decreases in GSH content resulting from the acetaldehyde attack to this critical antioxidant molecule were blamed by other workers to be responsible for a significant part of the ethanol-induced oxidative stress in other organs (Lu and Cederbaum, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…(Emanuele and Emanuele, 1997;Galvaõ-Teles et al, 1986;Garro et al, 1992;Gavaler, 1987;Mello et al, 1993;Mendelson and Mello, 1988;). Even more seriously, among alcoholic women, a teratogenic effect has been described, which has been named fetal alcohol syndrome (Garro et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…Some workers postulated that alcohol might lead to increased estrogen, inhibiting FSH and disrupting folliculogenesis and subsequently, the corpus luteum function. In addition, alcohol has been shown to suppress progesterone, the main secretion product of the corpus luteum (Garro et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Metabolism of ethanol to acetaldehyde and increased susceptibility to oxidative stress could play a role in the ovarian tissue cell injury promoted by alcohol drinking

et al. 2009

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It is known that drinking alcohol can lead to reproductive problems in women. In this study, we analyzed the possibility that part of those effects were mediated through alterations of ovarian function related to ethanol oxidation to acetaldehyde occurring in situ. Biotransformation in the rat ovary cytosolic fraction was partially inhibited by allopurinol, suggesting the participation of xanthine oxidoreductase in the process. Microsomal pathway was of enzymatic nature, requiring nicotinamide adenine dinucleotide phosphate-oxidase (NADPH), sensitive to oxygen and significantly inhibited by sodium diethyldithiocarbamate, 4-methylpyrazole and diphenyleneiodonium. Aldehyde dehydrogenase activity was detected by histochemistry in the ovarian tissue, in the strome surrounding the follicle while no alcohol dehydrogenase was detected. However, biochemical determination of alcohol dehydrogenase and aldehyde dehydrogenase activities in rat ovarian tissue revealed the presence of some activity of both enzymes but significantly lower than those found in the liver. By repetitive exposure of animals to ethanol, the microsomal metabolism to acetaldehyde was increased but not in the case of the cytosolic fraction. In these animals, t-butylhydroperoxyde-promoted chemiluminiscence was increased in comparison to control, revealing an increased susceptibility to oxidative stress due to alcohol drinking. Ultrastructure of ovarian tissue from rats exposed chronically to alcohol revealed alterations at the level of the granulosa; theca interna and pellucida zones. In the secondary follicle, alterations consisted of marked condensation of chromatin attached to the nuclear inner membrane. Intense dilatation of the outer perinuclear space could be observed. There was a marked dilatation of the rough endoplasmic reticulum accompanied of significant detachment of ribosomes from their membranes. Mitochondria appeared swollen. In the zona pellucida, most of the cell processes from oocyte and corona radiata cells were absent or broken totally or in part. Results suggest that in the rat ovary, metabolism of ethanol to acetaldehyde may play a role in alcohol effects on female reproductive function.

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Alcohol, vitamin A, and β-carotene: adverse interactions, including hepatotoxicity and carcinogenicity

Leo

Lieber

1999

The American Journal of Clinical Nutrition

241

152

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Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.

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Alcohol Abuse: Carcinogenic Effects and Fetal Alcohol Syndrome

Cited by 11 publications

References 284 publications

Liver Diseases by Alcohol and Hepatitis C: Early Detection and New Insights in Pathogenesis Lead to Improved Treatment

Liver Diseases by Alcohol and Hepatitis C: Early Detection and New Insights in Pathogenesis Lead to Improved Treatment

Metabolism of ethanol to acetaldehyde and increased susceptibility to oxidative stress could play a role in the ovarian tissue cell injury promoted by alcohol drinking

Alcohol, vitamin A, and β-carotene: adverse interactions, including hepatotoxicity and carcinogenicity

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