Identification and detoxification of glycolaldehyde, an unattended bioethanol fermentation inhibitor.

Although there have been approximately 60 chemical compounds identified as potent fermentation inhibitors in lignocellulose hydrolysate, our research group recently discovered glycolaldehyde as a key fermentation inhibitor during second generation biofuel production. Accordingly, we have developed a yeast S. cerevisiae strain exhibiting tolerance to glycolaldehyde. During this glycolaldehyde study, we established novel approaches for rational engineering of inhibitor-tolerant S. cerevisiae strains, including engineering redox cofactors and engineering the SUMOylation pathway. These new technical dimensions provide a novel platform for engineering S. cerevisiae strains to overcome one of the key barriers for industrialization of lignocellulosic ethanol production. As such, this review discusses novel biochemical insight of glycolaldehyde in the context of the biofuel industry.

ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde.

Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 µg/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence.

Increased levels of the acetaldehyde-derived DNA adduct N 2-ethyldeoxyguanosine in oral mucosa DNA from Rhesus monkeys exposed to alcohol.

Alcohol is a human carcinogen. A causal link has been established between alcohol drinking and cancers of the upper aerodigestive tract, colon, liver and breast. Despite this established association, the underlying mechanisms of alcohol-induced carcinogenesis remain unclear. Various mechanisms may come into play depending on the type of cancer; however, convincing evidence supports the concept that ethanol's major metabolite acetaldehyde may play a major role. Acetaldehyde can react with DNA forming adducts which can serve as biomarkers of carcinogen exposure and potentially of cancer risk. The major DNA adduct formed from this reaction is N (2)-ethylidenedeoxyguanosine, which can be quantified as its reduced form N (2)-ethyl-dG by LC-ESI-MS/MS. To investigate the potential use of N (2)-ethyl-dG as a biomarker of alcohol-induced DNA damage, we quantified this adduct in DNA from the oral, oesophageal and mammary gland tissues from rhesus monkeys exposed to alcohol drinking over their lifetimes and compared it to controls. N (2)-Ethyl-dG levels were significantly higher in the oral mucosa DNA of the exposed animals. Levels of the DNA adduct measured in the oesophageal mucosa of exposed animals were not significantly different from controls. A correlation between the levels measured in the oral and oesophageal DNA, however, was observed, suggesting a common source of formation of the DNA adducts. N (2) -Ethyl-dG was measured in mammary gland DNA from a small cohort of female animals, but no difference was observed between exposed animals and controls. These results support the hypothesis that acetaldehyde induces DNA damage in the oral mucosa of alcohol-exposed animals and that it may play role in the alcohol-induced carcinogenic process. The decrease of N (2)-ethyl-dG levels in exposed tissues further removed from the mouth also suggests a role of alcohol metabolism in the oral cavity, which may be considered separately from ethanol liver metabolism in the investigation of ethanol-related cancer risk.

SUMO expression shortens the lag phase of Saccharomyces cerevisiae yeast growth caused by complex interactive effects of major mixed fermentation inhibitors found in hot-compressed water-treated lignocellulosic hydrolysate.

The complex inhibitory effects of inhibitors present in lignocellulose hydrolysate suppress the ethanol fermentation of Saccharomyces cerevisiae. Although the interactive inhibitory effects play important roles in the actual hydrolysate, few studies have investigated glycolaldehyde, the key inhibitor of hot-compressed water-treated lignocellulose hydrolysate. Given this challenge, we investigated the interactive effects of mixed fermentation inhibitors, including glycolaldehyde. First, we confirmed that glycolaldehyde was the most potent inhibitor in the hydrolysate and exerted interactive inhibitory effects in combination with major inhibitors. Next, through genome-wide analysis and megavariate data modeling, we identified SUMOylation as a novel potential mechanism to overcome the combinational inhibitory effects of fermentation inhibitors. Indeed, overall SUMOylation was increased and Pgk1, which produces an ATP molecule in glycolysis by substrate-level phosphorylation, was SUMOylated and degraded in response to glycolaldehyde. Augmenting the SUMO-dependent ubiquitin system in the ADH1-expressing strain significantly shortened the lag phase of growth, released cells from G2/M arrest, and improved energy status and glucose uptake in the inhibitor-containing medium. In summary, our study was the first to establish SUMOylation as a novel platform for regulating the lag phase caused by complex fermentation inhibitors.

Identification of glycolaldehyde as the key inhibitor of bioethanol fermentation by yeast and genome-wide analysis of its toxicity.

Degradation of lignocellulose with pressurised hot water is an efficient method of bioethanol production. However, the resultant solution inhibits ethanol fermentation by Saccharomyces cerevisiae. Here, we first report that glycolaldehyde, which is formed when lignocellulose is treated with pressurised hot water, inhibits ethanol fermentation. The final concentration of glycolaldehyde formed by the treatment of lignocellulose with pressurised hot water ranges from 1 to 24 M, and 1-10 mM glycolaldehyde was sufficient to inhibit fermentation. This result indicates that glycolaldehyde is one of the main substances responsible for inhibiting fermentation after pressurised hot water degradation of lignocellulose. Genome-wide screening of S. cerevisiae revealed that genes encoding alcohol dehydrogenase, methylglyoxal reductase, polysomes, and the ubiquitin ligase complex are required for glycolaldehyde tolerance. These novel findings will provide new perspectives on breeding yeast for bioethanol production from biomass treated with pressurised hot water.

Simultaneous effects of nicotine, acrolein, and acetaldehyde on osteogenic-induced bone marrow cells cultured on plasma-sprayed titanium implants.

PURPOSE: To evaluate the potential interaction/contribution of inductive and deleterious effects of tobacco compounds on human osteoblastic cells cultured on plasma-sprayed titanium implants exposed to combinations of nicotine, acrolein, and acetaldehyde. Cell response was assessed as proliferation and function. MATERIALS AND METHODS: Titanium implants, seeded with human bone marrow-derived cells (first subculture), were cultured in osteogenic-inducing conditions for 28 days in the absence (control) and in the presence of tobacco compounds to assess (1) the dose-dependent profile of acrolein (0.01 to 0.12 mmol/L) and acetaldehyde (0.1 to 6 mmol/L) and (2) the effect of the simultaneous exposure to combinations of nicotine, acrolein, and acetaldehyde. In later experiments, seeded implants were exposed to two different concentrations of nicotine (1.2 mmol/L, known to have inductive effects on cell behavior, and 2.4 mmol/L, reported to elicit deleterious effects on cell behavior) with acrolein, acetaldehyde, or both, at a concentration that inhibits 50% (IC50). RESULTS: Acrolein and acetaldehyde caused dose-dependent inhibitory effects at levels similar to and greater than 0.03 and 0.1 mmol/L, respectively; IC50 regarding cell viability/proliferation and alkaline phosphatase was 0.06 mmol/L for acrolein and 0.3 mmol/L for acetaldehyde. Matrix mineralization was prevented at levels higher than 0.03 mmol/L acrolein and 0.1 mmol/L acetaldehyde. Exposure to a combination of nicotine 1.2 mmol/L with acrolein (0.06 mmol/L), acetaldehyde (0.3 mmol/L), or both resulted in a cell behavior intermediate to that observed in nicotine-treated cultures (induced cell response) and aldehyde-treated cultures (deleterious cell response). On the other hand, exposure to nicotine 2.4 mmol/L with acrolein (0.06 mmol/L), acetaldehyde (0.3 mmol/L), or both caused cumulative cytotoxic responses. CONCLUSION: Results suggest that interactions of tobacco compounds on osteoblasts might contribute to the overall effects of tobacco use on implant osseointegration and long-time survival.

The role of acetaldehyde outside ethanol metabolism in the carcinogenicity of alcoholic beverages: evidence from a large chemical survey.

Acetaldehyde is a volatile compound naturally found in alcoholic beverages, and it is regarded as possibly being carcinogenic to humans (IARC Group 2B). Acetaldehyde formed during ethanol metabolism is generally considered as a source of carcinogenicity in alcoholic beverages. However, no systematic data is available about its occurrence in alcoholic beverages and the carcinogenic potential of human exposure to this directly ingested form of acetaldehyde outside ethanol metabolism. In this study, we have analysed and evaluated a large sample collective of different alcoholic beverages (n=1,555). Beer (9+/-7 mg/l, range 0-63 mg/l) had significantly lower acetaldehyde contents than wine (34+/-34 mg/l, range 0-211 mg/l), or spirits (66+/-101 mg/l, range 0-1,159 mg/l). The highest acetaldehyde concentrations were generally found in fortified wines (118+/-120 mg/l, range 12-800 mg/l). Assuming an equal distribution between the beverage and saliva, the residual acetaldehyde concentrations in the saliva after swallowing could be on average 195 microM for beer, 734 microM for wine, 1,387 microM for spirits, or 2,417 microM for fortified wine, which are above levels previously regarded as potentially carcinogenic. Further research is needed to confirm the carcinogenic potential of directly ingested acetaldehyde. Until then, some possible preliminary interventions include the reduction of acetaldehyde in the beverages by improvement in production technology or the use of acetaldehyde binding additives. A re-evaluation of the 'generally recognized as safe' status of acetaldehyde is also required, which does not appear to be in agreement with its toxicity and carcinogenicity.

Interrelationship between alcohol, smoking, acetaldehyde and cancer.

In industrialized countries alcohol and tobacco are the main risk factors of upper digestive tract cancer. With regard to the pathogenesis of these cancers, there is strong epidemiological, biochemical and genetic evidence supporting the role of the first metabolite of alcohol oxidation--acetaldehyde--as a common denominator. Alcohol is metabolized to acetaldehyde locally in the oral cavity by microbes representing normal oral flora. Poor oral hygiene, heavy drinking and chronic smoking modify oral flora to produce more acetaldehyde from ingested alcohol. Also, tobacco smoke contains acetaldehyde, which during smoking becomes dissolved in saliva. Via swallowing, salivary acetaldehyde of either origin is distributed from oral cavity to pharynx, oesophagus and stomach. Strongest evidence for the local carcinogenic action of acetaldehyde provides studies with ALDH2-deficient Asian drinkers, who form an exceptional human model for long-term acetaldehyde exposure. After drinking alcohol they have an increased concentration of acetaldehyde in their saliva and this is associated with over 10-fold risk of upper digestive tract cancers. In conclusion, acetaldehyde derived either from ethanol or tobacco appears to act in the upper digestive tract as a local carcinogen in a dose-dependent and synergistic way.

Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde.

Strong epidemiological, genetic and biochemical evidence indicates that local acetaldehyde exposure is a major factor behind gastrointestinal cancers especially associated with alcohol drinking and smoking. Thus, reducing the exposure to carcinogenic acetaldehyde either by decreasing the production or by eliminating acetaldehyde locally might offer a preventive strategy against acetaldehyde-induced gastrointestinal cancers. Thiol products, such as the amino acid cysteine, are known to be able to protect against acetaldehyde toxicity. Cysteine is able to bind acetaldehyde efficiently by forming a stable thiazolidine-carboxylic acid compound. Special cysteine preparations (such as lozenge and chewing gum) have already been developed to bind smoking and alcohol drinking derived acetaldehyde from the oral cavity. Most importantly, these type of drug formulations offer a novel method for intervention studies aimed to resolve the eventual role of acetaldehyde in the pathogenesis of upper digestive tract cancers. Acetaldehyde exposure could also be influenced by modifying the acetaldehyde producing microbiota. With regard to the upper digestive tract, acetaldehyde production from ingested ethanol could be significantly reduced by using an antiseptic mouthwash, chlorhexidine. In the large intestine acetaldehyde production could be markedly decreased either by reducing the Gram-negative microbes by ciprofloxacin antibiotic or by lowering the intraluminal pH by lactulose.

Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration.

Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.

Alcohol consumption and cancer of the gastrointestinal tract.

Excessive alcohol consumption and heavy smoking are the main risk factors for upper digestive tract cancers. Cancer risk is dose-dependent and alcohol and smoking have synergistic effects. Alcohol is not carcinogenic. However, its first metabolite-acetaldehyde-has recently been shown to be a local carcinogen in humans. Microbes representing normal human gut flora are able to produce acetaldehyde from ethanol. This results in high local acetaldehyde concentrations in the saliva and contents of the large intestine. Asian heavy drinkers with a genetic deficiency for detoxifying acetaldehyde form an exceptional human 'knockout' model for long-term acetaldehyde exposure. The risk of alcohol-related digestive tract cancers is particularly high among this population. All mechanisms that have an effect on salivary or intracolonic acetaldehyde concentration are of importance. The message for prevention is that one should take care to have good oral hygiene and to avoid smoking, heavy drinking and drinking to intoxication.

Release of acid proteolytic activity from lysosomes and degradation of protein in organs of rats intoxicated with ethanol and acetaldehyde.

Intoxication with ethanol and acetaldehyde resulted in a marked increase of the acid proteolytic activity in the post-lysosomal supernatant of rat kidney, lung, and liver, while the content of protein and acid-soluble tyrosine remained practically unchanged. Proteins of the post-lysosomal supernatant were degraded in vitro by the endogenous proteinase(s) of lysosomal origin at pH 3.5 and 5.5 but not at pH 7.0.

Long-term toxicity and reproduction studies with metaldehyde in rats.

Rats received 0, 200, 1000 and 5000 ppm metaldehyde in the diet for 2 years. Reproduction studies over three generations using the same dietary levels were carried out. In the third litter of each generation attention was paid to possible embryotoxic or teratogenic effects. The parameters studied included growth, food intake, behaviour and survival, haematology, clinical biochemistry, organ weight, histopathology, reproductive performance and teratogenicity. At 5000 ppm the relative liver weight was increased and this was accompanied by an increase in liver microsomal enzyme activity. The most striking observation was a dose-related development of posterior paralysis in females due to a transverse lesion of the spinal cord. The latency period was more than 550 days. Three rats with posterior paralysis showed a transverse lesion of the spinal cord. No significant histological damage to other organs was seen. The tumour incidence was not increased in any of the metaldehyde dosage groups. The reproduction study confirmed the findings of the long-term test. Posterior paralysis appeared in at least 50% of the females on 5000 ppm metaldehyde in all 3 generations. Some were affected at 1000 ppm but none at 200 ppm. Histologically, a fracture or distortion of thoracic vertebrae and subsequent compression of the spinal cord was found. The onset of paralysis was related to the time of delivery. The reproductive performance was susceptibility in this respect to metaldehyde. Apart from one male rat on 200 ppm with clinical posterior paralysis without transverse lesions in the spinal cord, this level was without toxic effects both in the long-term and 3-generation reproduction study.

Mouthrinses with alcohol: cytotoxic effects on human gingival fibroblasts in vitro.

BACKGROUND: Mouthrinses are widely utilized in daily oral and dental hygiene to control plaque. However, most commercially available mouthrinses contain alcohol as an excipient. Most studies have focused on the clinical side effects related to the alcoholic fraction of mouthrinses, overlooking alcohol metabolism in the mouth. Due to this oral enzymatic process, the well-recognized toxic compound acetaldehyde is emitted in the mouth. Since gingival fibroblasts play a key role in oral connective tissue health maintenance, we investigated the effects of different doses of acetaldehyde on human gingival fibroblasts (HGFs) in order to better define the effects of alcohol-containing mouthrinses on oral tissue. METHODS: Cultured HGFs were exposed to different concentrations of acetaldehyde (10(-4) M to 10(-2) M). The cell adhesion rate was measured after a 3-hour incubation period, and cell viability over a 5-day period. In order to assess the reversibility of the damage produced by acetaldehyde, treatment was interrupted at critical doses (10(-3) M and 3 x 10(-3) M), and cell viability was evaluated on the third and fifth day of incubation. The HGF cytoskeleton was studied by immunocytochemical technique, and internal cell structures were observed with transmission electron microscopy to evaluate the morphological changes due to acetaldehyde. RESULTS: The results showed that acetaldehyde produced a dose- and time-dependent inhibition on cell adhesion and viability, together with disruption of cytoskeletal structures and cytoplasmic organelles. Nevertheless, these quantitative and qualitative damages were reversible when the treatment was interrupted. CONCLUSIONS: Although more knowledge is necessary, our results suggest that these deleterious effects may also occur in vivo. Pending further investigations, clinicians should be alerted to the potentially adverse effect of alcohol-containing mouthrinses and, to promote oral health, patients should be warned about improper use of these products.

Degradation in peritoneal dialysis fluids may be avoided by using low pH and high glucose concentration.

OBJECTIVE: When glucose is present in a medical fluid, the heat applied during sterilization leads to degradation. The glucose degradation products (GDPs) give rise to bioincompatible reactions in peritoneal dialysis patients. The extent of the degradation depends on a number of factors, such as heating time, temperature, pH, glucose concentration, and catalyzing substances. In the present work, we investigated the influence of pH and concentration in order to determine how to decrease the amounts of GDPs produced. DESIGN: Glucose solutions (1%-60% glucose; pH 1-8) were heat sterilized at 121 degrees C. Ultraviolet (UV) absorption, aldehydes, pH, and inhibition of cell growth (ICG) were used as measures of degradation. RESULTS: Glucose degradation was minimum at an initial pH (prior to sterilization) of around 3.5 and at a high concentration of glucose. There was considerable development of acid degradation products during the sterilization process when the initial pH was high. Two different patterns of development of UV-absorbing degradation products were seen: one below pH 3.5, dominated by the formation of 5-hydroxy-methyl-2-furaldehyde (5-HMF); and one above, dominated by degradation products absorbing at 228 nm. 3-Deoxyglucosone (3-DG) concentration and the portion of 228 nm UV absorbance not caused by 5-HMF were found to relate to the in vitro bioincompatibility measured as ICG; there was no relation between 5-HMF or absorbance at 284 nm and bioincompatibility. CONCLUSION: In order to minimize the development of bioincompatible GDPs in peritoneal dialysis fluids during heat sterilization, pH should be kept around 3.2 and the concentration of glucose should be high. 5-HMF and 284 nm UV absorbance are not reliable as quality measures. 3-DG and the portion of UV absorbance at 228 nm caused by degradation products other than 5-HMF seem to be reliable indicators of bioincompatibility.

Photodegradation of gaseous acetaldehyde and methylene blue in aqueous solution with titanium dioxide-loaded activated carbon fiber polymer materials and aquatic plant ecotoxicity tests.

TiO2-supported activated carbon felts (TiO2-ACFTs) were prepared by dip coating of felts composed of activated carbon fibers (ACFs) with either polyester fibers (PS-A20) and/or a polyethylene pulp (PE-W15) in a TiO2 aqueous suspension followed by calcination at 250 °C for 1 h. The as-prepared TiO2-ACFTs with 29-35 wt.% TiO2 were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and N2 adsorption. The TiO2-ACFT(PS-A20) samples with 0 and 29 wt.% TiO2 were microporous with specific surface areas (S BET) of 996 and 738 m(2)/g, respectively, whereas the TiO2-ACFT(PE-W15) samples with 0 and 35 wt.% TiO2 were mesoporous with S BET of 826 and 586 m(2)/g, respectively. Adsorption and photocatalytic activity of the as-prepared samples were evaluated by measuring adsorption in the dark and photodegradation of gaseous acetaldehyde (AcH) and methylene blue (MB) in aqueous solution under UV light. The TiO2 loading caused a considerable decrease in the S BET and MB adsorption capacity along with an increase in MB photodegradation and AcH mineralization. Lemna minor was chosen as a representative aquatic plant for ecotoxicity tests measuring detoxification of water obtained from the MB photodegradation reaction with the TiO2-ACFT samples under UV light.

Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism.

BACKGROUND: An increasing body of evidence now implicates acetaldehyde as a major underlying factor for the carcinogenicity of alcoholic beverages and especially for oesophageal and oral cancer. Acetaldehyde associated with alcohol consumption is regarded as 'carcinogenic to humans' (IARC Group 1), with sufficient evidence available for the oesophagus, head and neck as sites of carcinogenicity. At present, research into the mechanistic aspects of acetaldehyde-related oral cancer has been focused on salivary acetaldehyde that is formed either from ethanol metabolism in the epithelia or from microbial oxidation of ethanol by the oral microflora. This study was conducted to evaluate the role of the acetaldehyde that is found as a component of alcoholic beverages as an additional factor in the aetiology of oral cancer. METHODS: Salivary acetaldehyde levels were determined in the context of sensory analysis of different alcoholic beverages (beer, cider, wine, sherry, vodka, calvados, grape marc spirit, tequila, cherry spirit), without swallowing, to exclude systemic ethanol metabolism. RESULTS: The rinsing of the mouth for 30 seconds with an alcoholic beverage is able to increase salivary acetaldehyde above levels previously judged to be carcinogenic in vitro, with levels up to 1000 µM in cases of beverages with extreme acetaldehyde content. In general, the highest salivary acetaldehyde concentration was found in all cases in the saliva 30 sec after using the beverages (average 353 µM). The average concentration then decreased at the 2-min (156 µM), 5-min (76 µM) and 10-min (40 µM) sampling points. The salivary acetaldehyde concentration depends primarily on the direct ingestion of acetaldehyde contained in the beverages at the 30-sec sampling, while the influence of the metabolic formation from ethanol becomes the major factor at the 2-min sampling point. CONCLUSIONS: This study offers a plausible mechanism to explain the increased risk for oral cancer associated with high acetaldehyde concentrations in certain beverages.

A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.

The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 µM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 µmol/l, p<0.05) and without (258 vs. 89 µmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure.

Increased salivary acetaldehyde levels in heavy drinkers and smokers: a microbiological approach to oral cavity cancer.

The pathogenetic mechanisms behind alcohol-associated carcinogenesis in the upper digestive tract remain unclear, as alcohol is not carcinogenic. However, there is increasing evidence that a major part of the tumour-promoting action of alcohol might be mediated via its first, toxic and carcinogenic metabolite acetaldehyde. Acetaldehyde is produced from ethanol in the epithelia by mucosal alcohol dehydrogenases, but much higher levels derive from microbial oxidation of ethanol by the oral microflora. In this study we investigated factors that might alter the composition and quantities of the oral microflora and, consequently, influence microbial acetaldehyde production. Information about dental health, smoking habits, alcohol consumption and other factors was obtained by a questionnaire from 326 volunteers with varying social backgrounds and health status, e.g. oral cavity malignancy. Paraffin-induced saliva was collected and the microbial production of acetaldehyde from ethanol was measured. Smoking and heavy drinking were the strongest factors increasing microbial acetaldehyde production. Whether poor dental status may alter local acetaldehyde production from ethanol remained unanswered. Bacterial analysis revealed that mainly gram-positive aerobic bacteria and yeasts were associated with higher acetaldehyde production. Increased local microbial salivary acetaldehyde production due to ethanol among smokers and heavy drinkers could be a biological explanation for the observed synergistic carcinogenic action of alcohol and smoking on upper gastrointestinal tract cancer. It offers a new microbiological approach to ethanol-associated carcinogenesis at these anatomic sites.