Interaction of Alcohol and Smoking in the Pathogenesis of Upper Digestive Tract Cancers − Possible Chemoprevention with Cysteine
نویسندگان
چکیده
.. ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 8 INTRODUCTION ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 10 REVIEW OF THE LITERATURE ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 12 1 Epidemiology of upper digestive tract cancers ... .... ... ... ... ... ... ... ... ... ... ... ... . 13 1.1 Alcohol and upper digestive tract cancers ... ... ... ... ... ... ... ... ... ... ... ... ... . 13 1.1.1 Mouth and pharynx ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 14 1.1.2 Larynx ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 14 1.1.3 Oesophagus ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 15 1.1.4 Stomach ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 16 1.2 Synergistic effect of alcohol and tobacco on upper digestive tract cancers .. 18 1.2.1 Mouth and pharynx ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 19 1.2.2 Larynx ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 19 1.2.3 Oesophagus ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 20 1.2.4 Stomach ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 21 1.3 Effect of gene polymorphism on alcohol-related upper digestive tract cancers 22 1.3.1 ALDH-polymorphism ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 22 1.3.2 ADH-polymorphism ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 23 2 Ethanol metabolism in the gastrointestinal tract ... ... ... ... ... ... ... ... ... ... ... ... ... . 24 2.1 Distribution of ethanol ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 24 2.2 Ethanol and acetaldehyde metabolism ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 24 2.2.1 Alcohol dehydrogenase ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 25 2.2.2 MEOS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 25 2.2.3 Catalase ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 26 2.2.4 Aldehyde dehydrogenase ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 26 2.3 Microbial ethanol metabolism ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 27 3 Ethanol and acetaldehyde as carcinogenic substances ... ... ... ... ... ... ... ... ... ... ... . 28 3.1 Ethanol ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 28 3.2 Acetaldehyde ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 29 3.2.1 Acetaldehyde-related experimental toxicity ... ... ... ... ... ... ... ... ... 30 3.2.2 Acetaldehyde-related carcinogenicity in experimental animals ... .. 32 3.2.3 Acetaldehyde-related carcinogenicity in humans ... ... ... ... ... ... ... 33 3.3 Tobacco smoking and acetaldehyde ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 35 4 Regulation of local acetaldehyde concentration in the upper digestive tract ... ... .. 37 4.1 Role of microbes and oral hygiene ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 37 4.2 Role of genetic factors ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 39 4.3 Role of tobacco smoking ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 40 4.4 Role of cysteine as an acetaldehyde-binding agent ... ... ... ... ... ... ... ... ... ... 41 4.4.1 Interaction of acetaldehyde and cysteine ... ... ... ... ... ... ... ... ... ... . 41 4.4.2 Problems related to the in vivo use of cysteine ... ... ... ... ... ... ... ... 43 AIMS OF THE STUDY ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 45 MATERIALS AND METHODS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 46 1 Acetaldehyde production and ethanol oxidation by Escherichia coli (I) ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .... 46 2 Effect of alcohol drinking and smoking on salivary acetaldehyde (II) ... ... ... .. 47 3 Binding of salivary acetaldehyde by L-cysteine during alcohol metabolism (III) ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 48 4 Binding of salivary acetaldehyde by L-cysteine during smoking (IV) ... ... ... .. 49 5 Measurement of acetaldehyde and ethanol by gas chromatograph ... ... ... ... .... 50 6 Statistical analysis ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 51 7 Ethical considerations ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... . 51 RESULTS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 52 1 ADH-dependent acetaldehyde formation of Escherichia coli in different oxygen tensions (I) ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 52 2 Synergistic effect of alcohol drinking and smoking on acetaldehyde concentration in saliva (II) ...... ... ... ... ... ... ... ... ... ... ... ... ... .... 53 3 Ability of slow-releasing L-cysteine tablet to bind acetaldehyde in saliva during alcohol metabolism (III) ..... ... ... ... ... ... ... ... ... ... ... ... ... ... 54 4 Elimination of acetaldehyde from saliva by L-cysteine sucking tablet during smoking (IV) .... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 54 DISCUSSION ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 56 1 Experimental evidence of microbial acetaldehyde production under different atmospheric conditions prevailing in the digestive tract ...... ... ... ... ... 56 2 Multiplicative exposure to carcinogenic acetaldehyde behind the synergistic effect of alcohol and tobacco on cancer risk ... ... ... ... ... ... ... ... ... 57 3 Reducing exposure of the upper digestive tract to carcinogenic acetaldehyde by L-cysteine after alcohol consumption ..... ... ... ... ... ... ... ... ... 59 4 Reducing exposure to carcinogenic acetaldehyde by L-cysteine during smoking ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 60 SUMMARY AND CONCLUSIONS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... .. 61 ACKNOWLEDGEMENTS ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 63 REFERENCES ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... ... 64
منابع مشابه
Short Communication Eliminating Carcinogenic Acetaldehyde By Cysteine From Saliva During Smoking
Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity. We developed a tablet that releases cysteine into the oral cavi...
متن کاملEliminating carcinogenic acetaldehyde by cysteine from saliva during smoking.
Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity. We developed a tablet that releases cysteine into the oral cavi...
متن کاملAn Ecological Study of the Association between Opiate Use and Incidence of Cancers
Background: Cancer is the second leading cause of death after cardiovascular disease. In recent years it has been hypothesized that opiate use could be a risk factor for cancer. This study aimed to evaluate a possible association between opiate use and common cancers using ecological statistics from around the world.Methods: To investigate the association we used ordinary linear regression mode...
متن کاملAlcohol, tobacco and genetic susceptibility in relation to cancers of the upper aerodigestive tract in northern Italy.
AIMS AND BACKGROUND Each year in Italy there are approximately 14,000 new cases and 7,000 deaths from cancer of the upper aerodigestive tract, which includes malignant tumors originating from the oral cavity, pharynx, larynx and esophagus. Established etiological factors include tobacco consumption and heavy alcohol drinking. The study of single nucleotide polymorphisms in upper aerodigestive t...
متن کاملCigarettes and Gastrointestinal Disorders
Background and Objectives: Smoking is an important risk factor for gastrointestinal disorders such as peptic ulcer, Crohn's disease and various cancers. The present study discusses the most important and known effects of smoking on the gastrointestinal tract. Method and Materials: This review uses the keywords Smoking, Gastrointestinal diseases, Inflammation and Cancer in the English database...
متن کامل