High Salivary Acetaldehyde After a Moderate Dose of Alcohol in ALDH2‐Deficient Subjects: Strong Evidence for the Local Carcinogenic Action of Acetaldehyde

Väkeväinen, Satu; Tillonen, Jyrki; Agarwal, D. P.; Srivastava, Nidhi; Salaspuro, Mikko

doi:10.1111/j.1530-0277.2000.tb02068.x

Cited by 177 publications

(82 citation statements)

References 25 publications

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“…8 Our recent findings demonstrate that Asians with this mutant ALDH2 have 2-3 times higher salivary acetaldehyde levels after a moderate dose of ethanol than Asians with the normal ALDH2 enzyme. 7 When this observation is combined with the earlier epidemiologic data, our results provide strong evidence for the local carcinogenic action of acetaldehyde produced from alcohol in the saliva by either oral microbes or in the salivary glands.…”

supporting

confidence: 73%

“…notype. 7,36 Hence, there is conclusive experimental evidence of the local carcinogenic action of acetaldehyde in humans.…”

Section: Discussionmentioning

confidence: 99%

“…10,37 This reaction leads to the formation of marked amounts of acetaldehyde in the saliva by oral microflora after the ingestion of a moderate amount of alcohol. 7 Salivary acetaldehyde production can be significantly reduced by the use of an antiseptic mouthwash, underlying the microbial background for local acetaldehyde production. 19 Furthermore, in vitro acetaldehyde production by mouthwashings from oropharyngolaryngeal cancer patients has been shown to be significantly higher than that of the control patients, 11 and the production of acetaldehyde in saliva from ethanol is markedly increased in smokers and heavy drinkers.…”

Section: Discussionmentioning

confidence: 99%

“…Acetaldehyde, the first metabolite of ethanol, has been shown to be carcinogenic in animals and there exists strong evidence of its carcinogenic action also in man. 6,7 Asian heavy drinkers with a genetically deficient aldehyde dehydrogenase (ALDH2) enzyme do show a markedly increased risk for GI-tract cancers. 8 Our recent findings demonstrate that Asians with this mutant ALDH2 have 2-3 times higher salivary acetaldehyde levels after a moderate dose of ethanol than Asians with the normal ALDH2 enzyme.…”

Section: Abstract: Acetaldehyde; L-cysteine; Upper Digestive Tract; mentioning

confidence: 99%

“…15 Thereby, cysteine could prevent acetaldehyde to interact with cellular proteins and DNA, which might interfere with normal cellular functions including acetaldehydeinduced carcinogenesis. 6,7,16,17 The aim of our study was to examine the ability of L-cysteine, which was slowly released from a special drug formulation, to bind salivary acetaldehyde in the oral cavity after the ingestion of a dose of alcohol and thus to reduce the potential carcinogenic effects of topical acetaldehyde in the upper gastrointestinal tract. …”

mentioning

confidence: 99%

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Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

Salaspuro

Hietala

Kaihovaara

et al. 2001

Intl Journal of Cancer

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High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL 95% 43%, 76%). Area under the curve (AUC 0 -320min ) with the L-cysteine and placebo tablet were 54.3 ؎ 11 M ؋ hr and 162 ؎ 34.2 M ؋ hr (mean ؎ SEM), respectively (p ‫؍‬ 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow-releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals. © 2002 Wiley-Liss, Inc. Key words: acetaldehyde; L-cysteine; upper digestive tract; carcinogenesisAlcohol intake and tobacco smoking are the most important independent risk factors for upper digestive tract cancers. [1][2][3][4][5] Many of the compounds in the tobacco smoke are carcinogenic, but, in contrast, the tumour-promoting effects of alcohol drinking has so far been less well defined. Acetaldehyde, the first metabolite of ethanol, has been shown to be carcinogenic in animals and there exists strong evidence of its carcinogenic action also in man. 6,7 Asian heavy drinkers with a genetically deficient aldehyde dehydrogenase (ALDH2) enzyme do show a markedly increased risk for GI-tract cancers. 8 Our recent findings demonstrate that Asians with this mutant ALDH2 have 2-3 times higher salivary acetaldehyde levels after a moderate dose of ethanol than Asians with the normal ALDH2 enzyme. 7 When this observation is combined with the earlier epidemiologic data, our results provide strong evidence for the local carcinogenic action of acetaldehyde produced from alcohol in the saliva by either oral microbes or in the salivary glands.After absorption, ethanol is evenly distributed to the waterphase of the body, and ethanol concentration in the saliva equals that of the blood. 9 In addition to the tissue alcohol ...

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supporting

confidence: 73%

“…notype. 7,36 Hence, there is conclusive experimental evidence of the local carcinogenic action of acetaldehyde in humans.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Abstract: Acetaldehyde; L-cysteine; Upper Digestive Tract; mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

Salaspuro

Hietala

Kaihovaara

et al. 2001

Intl Journal of Cancer

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Exploring the link between microorganisms and oral cancer: A systematic review of the literature

2009

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The majority of cases of oral cancer have been related to tobacco use and heavy alcohol consumption. However, the incidence of oral cavity carcinoma appears to be increasing in many parts of the world in a manner that it is difficult to explain with traditional risk factors alone. Meanwhile, interest in the possible relationships between microorganisms and the different stages of cancer development has been rising and numerous mechanisms by which bacteria and yeast may initiate or promote carcinogenesis are currently under investigation. In particular, a persuasive body of evidence suggests a possible etiological role involving the metabolism and production of carcinogenic products, such as acetaldehyde. Other suggested mechanisms include the induction of chronic inflammation and direct interference with eukaryotic cell cycle and signaling pathways. This review aims to summarize the known associations between microbial infection and cancer and draw attention to how they may relate to oral carcinoma.

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Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics

Seitz

Stickel

Homann

2003

Intl Journal of Cancer

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Chronic excessive alcohol consumption is the strongest risk factor for upper aerodigestive tract (UADT) cancer (oral cavity, pharynx, hypopharynx, larynx, esophagus). 1 In addition, alcohol also increases the risk for cancer of the liver, colorectum and breast. 1 A great number of epidemiological studies have demonstrated a correlation between alcohol ingestion and the occurrence of cancer in these organs. [1][2][3][4][5][6][7][8][9] These studies clearly show that the ingestion of all types of alcoholic beverages is associated with an increased cancer risk that suggests that ethanol itself is the crucial compound that causes that effect. The exact mechanism(s) of ethanol-associated carcinogenesis has remained obscure because ethanol by itself when given to animals is not carcinogenic. 10 Multiple mechanisms are involved in alcohol-associated cancer development of the UADT including the effect of acetaldehyde (AA), the first metabolite of ethanol oxidation, induction of cytochrome P-4502E1 (CYP2E1) leading to the generation of reactive oxygen species (ROS) and enhanced procarcinogen activation, modulation of cellular regeneration and nutritional deficiencies.In our minireview, major emphasis is laid on more recent developments including genetic aspects of ethanol metabolism, bacterial alcohol oxidation and nutritional deficiencies. EPIDEMIOLOGYAs early as at the beginning of the last century, Lamu noticed an increased incidence of esophageal cancer in absinth drinkers. 11 Meanwhile, an extensive body of epidemiologic data has accumulated that identified alcohol as a major risk factor for UADT cancer. [1][2][3][4][5][6] In a carefully designed French study, Tuyns 2 was able to demonstrate that alcohol consumption of more than 80 g/day (ϳ1 bottle of wine) increases the relative risk (RR) of esophageal cancer by a factor of 18, whereas smoking only (more than 20 cigarettes) leads to an increased RR of 5. Both factors act synergistically, resulting in an increased RR of 44. 2 More recently, an epidemiologic study by Maier et al. 3 showed that 90% of all patients with head and neck cancer consumed alcohol regularly in quantities twice the amount of a control group with a significant dose-response relationship. If the RR for an individual with a daily alcohol consumption of 25 g was assumed to be 1, this figure rose to 32 if alcohol consumption exceeded 100 g. Bruguere et al. 5 found RR values of 13.5 for oral cancer, 15.2 for oropharyngeal carcinoma, and of 28.6 for hypopharyngeal carcinoma when 100 -159 g of alcohol were consumed daily. It is noteworthy that even with these high daily alcohol dosages, the alcohol-associated cancer risk is not saturable. Alcohol consumption exceeding 1.5 bottles of wine daily results in a 100-fold increased risk for esophageal cancer. 4 In an epidemiologic study of the American Cancer Society on more than 750,000 individuals, Bofetta and Garfinkel 12 found an increased risk for esophageal cancer already at a dose of 12 g alcohol daily (RR ϭ 1.37) rising to an RR ϭ 5.8 after 72 g al...

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High Salivary Acetaldehyde After a Moderate Dose of Alcohol in ALDH2‐Deficient Subjects: Strong Evidence for the Local Carcinogenic Action of Acetaldehyde

Cited by 177 publications

References 25 publications

Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

Exploring the link between microorganisms and oral cancer: A systematic review of the literature

Pathogenetic mechanisms of upper aerodigestive tract cancer in alcoholics

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