Institute of Biochemistry, National Academy of Sciences of Belarus, Laboratory of Alcohol and Aldehyde Biochemistry, Grodno 230017, Belarus and
1 Grodno State Medical University, Grodno, 230015, Belarus
Received 11 May 2001; in revised form 20 November 2001; accepted 3 December 2001
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ABSTRACT |
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INTRODUCTION |
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Prospective studies have shown increased incidence of rectal cancer in subjects consuming alcohol regularly (Kune and Vitetta, 1992; Seitz and Pöschl, 1997
). The accumulation of acetaldehyde in the colon during ethanol metabolism has been suggested to be at least partly responsible for colorectal cancer associated with alcohol consumption (Seitz et al., 1990
; Simanowski et al., 1994). However, no comprehensive studies have been done on enzymes producing acetaldehyde nor ALDH in the rectum of the rat. In the present study, we examined the effect of chronic alcohol consumption on the activities of ADH, MEOS, catalase and ALDH in the mucosa of different regions of the GIT with a view to estimating the possible contribution of the ethanol- and acetaldehyde-metabolizing systems to the local accumulation of acetaldehyde and toxic ethanol effects in the GIT.
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MATERIALS AND METHODS |
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The daily dietary intake of control and alcohol diets was approximately the same (455.6 ± 11.7 and 424.1 ± 12.9 g/kg body weight/day, respectively), as well as the weight gain during the 30-day treatment. In the control group, body weight increased from 173.9 ± 2.5 to 243.8 ± 5.8 g and in the experimental group the increase was from 174.5 ± 2.6 to 232.0 ± 4.3 g. The consumption of ethanol per day fluctuated from 10 to 14.5 g/kg body weight, with a mean of 11.4 g/kg body weight per day during the treatment period. The experimental animals were found to be ethanol-intoxicated, the extent of the intoxication being similar to that after administration of a low or moderate dose of alcohol and the diurnal blood-ethanol levels fluctuated from 2.2 to 16.7 mM (1077 mg/dl). The following mean blood-ethanol concentrations (± SEM) were found: at 09:00, 11.3 ± 4.6 mM; at 15:00, 2.3 ± 0.5 mM; and at 21:00, 5.9 ± 3.0 mM.
One month after the start of the experiment, the group of rats receiving the ethanol diet (n = 9) and that receiving the control diet (n = 9) were given a 2 g/kg body weight dose of ethanol intragastrically. One hour later, the rat abdominal cavities were opened under hexenal anaesthesia (90 mg/kg, intraperitoneally), and samples of the contents of the stomach, small intestine, colon and rectum were collected and immediately frozen in liquid nitrogen. The samples were homogenized with 4 volumes of 0.6 M perchloric acid and 0.5 mM thiourea solution at 04°C and the supernatants after centrifugation were used for ethanol and acetaldehyde determination by gas chromatography as described earlier (Pronko et al., 1993).
Assay of enzyme activities
For enzyme activity determination, the rats were decapitated after overnight starvation. Their peritoneal cavity was opened and the stomach, small and large intestines (caecum, colon and rectum) were removed. The samples were washed in a cooled isotonic sodium chloride solution, dried with filter paper and the mucosal layer was separated with a scalpel. Subsequently, the mucosa was either used for isolation of fractions or frozen in liquid nitrogen in which the samples were stored until examination. ADH dehydrogenase activity was assayed in the post-mitochondrial supernatant (20 000 g, 1 h) in 100 mM glycine buffer (pH 9.6) containing 1 mM NAD and 25 mM of ethanol. NADH formation was measured spectrophotometrically at 340 nm at 25°C, by the method of Koivisto and Salaspuro (1996). Reductase activity of ADH was determined in 100 mM phospate buffer (pH 6.4) containing 1 mM of NADH and 5 mM acetaldehyde at 25°C, by measuring the decrease of NADH. The microsomal fraction was isolated according to Stohs et al. (1976). MEOS activity was determined by the method of Seitz et al. (1979). The peroxisome-enriched -fraction was isolated by the method of Antonenkov et al. (1982). The peroxidatic activity of catalase was determined in 0.1 M phosphate buffer (pH 7.4) containing peroxisomal protein, 15 mM semicarbazideHCl and 50 mM ethanol at 37°C. After 10 min of preincubation the reaction was initiated by addition of 10 mM H2O2 and stopped after 10 min by addition of 2 ml 0.6 M perchloric acid. The acetaldehyde formed was determined gas chromatographically (Pronko et al., 1993
). ALDH activity was assayed spectrophotometrically (Lamboeuf et al., 1981
; Koivisto and Salaspuro, 1996
) with 5 mM and 100 µM acetaldehyde as substrates at 37°C. Protein was determined according to the method of Lowry et al. (1951).
Histological study
For histological studies, samples of the oesophagus, fundus and pyloric regions of the stomach, the jejunum, the transverse colon, the caecum and the rectum from control and experimental group animals were fixed in a 10% neutral formalin, dehydrated in alcohol, cleared in xylene and mounted in paraffin wax. Sections 7 µm thick were stained with haematoxylin and eosin and mounted on polystyrene. The histological preparations were examined using a light microscope.
Statistical analysis
The results are expressed as means ± SEM. Unpaired Student's t-test was used to determine the significance of the differences between the means of the values obtained from the experimental groups and those obtained from the control groups.
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RESULTS |
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DISCUSSION |
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The reductase activity of ADH in the GIT of control and alcohol-treated animals, as well as the dehydrogenase activity of the enzyme, ranged in the following decreasing order: rectum, stomach, colon and small intestine. The ADH reductase activity was 510-fold higher than the ADH dehydrogenase activity (Table 1). This is in agreement with the established fact that ADH is much better suited for aldehyde reduction, especially at neutral pH. At maximal velocity, the rate of acetaldehyde reduction is
40-fold greater than the rate of alcohol oxidation for the enzyme from human liver (Pietruszko, 1979
). The activities of rat liver ADH isoenzymes determined with acetaldehyde as a substrate were several-fold higher compared to the activities determined with ethanol (Mezey and Potter, 1983
). The MichaelisMenten constants for ethanol were 3.38.6-fold higher than that for acetaldehyde for different isoenzymes of the enzyme studied (Mezey and Potter, 1983
).
The relatively high dehydrogenase activity of ADH in the rectum (2.6-fold higher compared to the stomach and 2.2-fold higher compared to the colon) can cause an increase in the level of acetaldehyde after alcohol treatment and may play a role in ethanol-dependent injury of the rectal mucosa. Besides, it should be taken into consideration that ADH of bacteria inhabiting the large intestine of humans and rats can also oxidize ethanol, causing production of high concentrations of reactive and toxic acetaldehyde (Seitz et al., 1990; Jokelainen et al., 1996
, 1997
).
In the control rats, the activity of MEOS was significantly higher in rectal mucosa, compared to the small intestines and colon. MEOS activity levels in the small intestine (0.75 ± 0.24 nmol of acetaldehyde/min/mg) were close to those determined by the authors of the method (Seitz et al., 1979) (0.407 ± 0.058 nmol of acetaldehyde/min/mg). However, Seitz et al. (1982) found lower MEOS activity in the colon, compared to values reported in the present work for rectal mucosa. Partly it may be explained by the fact that the MEOS activity in the rectum was 2.5-fold higher compared to the colon (Table 2
). After consumption of the alcohol diet, we observed a statistically significant increase in MEOS activity only in the stomach. This is in line with the information that chronic ethanol consumption causes an induction of cytochrome P450 2E1 in the mucosa of the upper GIT regions of rats (Shimizu et al., 1990
) and that such treatment has no effect on colonic MEOS activity (Seitz et al., 1982
). We found that MEOS activity in the small intestine of rats consuming ethanol diet was 25% higher, compared to rats on the control diet, but the difference was not statistically significant. Earlier, an increase in ethanol oxidation by small intestinal microsomes (Seitz et al., 1979
) and an induction of CYP2E1 in rat colon after alcohol feeding (Hakkak et al., 1996
) were reported. The adequate carbohydrate content of the liquid alcohol diet used in our experiment (35%) possibly explains this discrepancy. It is known that high induction of the MEOS and hepatic microsomal CYP2E1 by ethanol can be achieved with a low carbohydrate (Teschke et al., 1981
) or carbohydrate-deficient (2.5%) diet (Korourian et al., 1999
). MEOS activity in the GIT, including rectum, possibly contributes to ethanol oxidation in order to produce acetaldehyde and free radicals playing an important role in the pathogenesis of various alcoholic injuries (French et al., 1993
; Albano et al., 1994
).
It should be noted that there are no literature data on alcohol metabolism by the peroxidatic reaction of catalase in the mucosa of the GIT. Previously some authors observed only catalase activity of this enzyme by measuring the decrease in hydrogen peroxide during the reaction (Beno et al., 1994; Salmela et al., 1996
). The latter authors, determining catalase activity in vitro, concluded that rat catalase, in addition to ADH, may play a significant role in gastric ethanol metabolism. As our studies showed, the peroxidatic activity of catalase was higher in the rectum of rats consuming the control diet. An exogenous supply of ethanol with the liquid diet activated the catalase peroxidatic reaction in the rectum and possibly increased its contribution to alcohol metabolism.
The histochemical studies of Chieco et al. (1998) have shown that activity of ALDH with acetaldehyde as substrate in mM concentrations is much lower in the large intestine than in the stomach and small intestine. According to the data of Koivisto and Salaspuro (1996) the high KM ALDH activity was significantly lower in the colon than in the upper parts of the GIT. Our results expand these data, as we have found relatively low ALDH activity both in the rectal mucosa and in the colon at both µM and mM concentrations of acetaldehyde.
It is of interest that, in the rectum, low ALDH activity is associated with the highest activity of ADH and catalase, as compared with other regions of the GIT. In our experiment, chronic alcohol consumption produced a significant decrease of low KM ALDH activity and in addition an activation of catalase and MEOS in the rectum of rats. The low-activity ALDH cannot possibly compensate for acetaldehyde production by relatively high ADH, peroxidatic catalase and MEOS activities in the mucosa of large intestine, and this may contribute to local acetaldehyde accumulation in the large intestine of alcohol-treated animals equally with acetaldehyde produced by intestinal microflora. This assumption is supported by our data: acute alcohol intoxication produced significantly higher acetaldehyde concentrations in the contents of the colon and rectum of rats receiving alcohol chronically, as compared to the controls. We did not measure the acetaldehyde concentrations in the mucosa of the various gastrointestinal segments. However, it was demonstrated that the concentration of acetaldehyde in rat colonic mucosa was higher than that in liver and blood after an acute dose of ethanol. The acetaldehyde levels were significantly higher in the rectum compared to the caecum; chronic ethanol consumption, however, did not influence them (Seitz et al., 1990).
Our data obtained in the rat could be extrapolated to the human situation with limitations, since ADH isoenzymes differ between rodents and man. However, some features of the distribution of activities of alcohol- and aldehyde-metabolizing enzymes along the GIT, as well as the morphological changes observed in the GIT after ethanol consumption, are very similar in rat and man. We observed significantly higher ADH activity in rat rectal mucosa, compared to colon. The same correlation of ADH activities in colon and rectum has been described for humans (Seitz et al., 1996). In the rat, ALDH activities of colonic mucosa were lower when compared with the liver and stomach (Koivisto and Salaspuro, 1996
). We found that low- and high-KM ALDH activities in rat colon and rectum were significantly lower, compared to those in the stomach and small intestine. The above data are in good agreement with the information that the overall ALDH activity of human rectal mucosa was considerably lower than that reported for liver (Agarwal et al., 1997
). These findings are of interest with respect to the fact that heavy drinking results in an increased rectal cancer risk, but to a lesser extent colon cancer risk (Kune and Vitetta, 1992
).
It is known that alcohol misuse by humans contributes to the development of cancers of the oropharynx, oesophagus, liver and rectum (Shimizu et al., 1990; Maier et al., 1994a
; Seitz et al., 1998
). Ethanol itself is not a carcinogen, but, under certain experimental conditions, it acts as a co-carcinogen and a tumour promoter (Seitz et al., 1998
). At the same time, its metabolite acetaldehyde is regarded as a mutagen and a carcinogen capable of damaging DNA molecules (Fang and Vaca, 1995
). Our morphological studies on chronically intoxicated rats produced findings similar to those previously observed in rats (Simanowski et al., 1993
, 1994; Maier et al., 1994b
). The data from the rat model confirm previous findings in humans. Thus, chronic alcohol misuse in heavy drinkers leads to rectal mucosal hyperproliferation (Simanowski et al., 2001
). These morphologic changes are possibly related to an increased production of reactive and toxic acetaldehyde, which may lead to mucosal damage and to secondary compensatory hyper-regeneration (Seitz et al., 1990
). This suggestion is supported by the fact that acetaldehyde intake with drinking water also produced hyperplastic and hyperproliferative changes in the upper regions of the GIT (Cai and Wei, 1996
; Homann et al., 1997
).
Thus, in the rat the unfavourable correlation between the relatively high activities of acetaldehyde-producing enzymes and relatively low activities of acetaldehyde-oxidizing enzymes in the large intestinal regions is aggravated after chronic alcohol consumption. The decreased activity of low-KM ALDH in alcohol-fed animals associated with increased or unaltered activities of ADH, catalase and MEOS in the mucosa of the colon and especially of the rectum results in an imbalance between the production and disposition of acetaldehyde. The latter causes elevated levels of acetaldehyde in the lumen of these portions of the intestine after chronic alcohol consumption. This mechanism can account for the local toxicity of ethanol when consumed chronically and relates the development of mucosal damage and compensatory hyper-regeneration processes (possibly involved in carcinogenesis) in colonic and rectal mucosa to the effect of acetaldehyde.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Albano, E., Tomasi, A. and Ingelman-Sundberg, M. (1994) Spin trapping of alcohol derived radicals in microsomes and reconstituted systems by electron spin resonance. Methods in Enzymology 223, 117127.
Antonenkov, V. D., Salnikov, Yu. A. and Panchenko, L. F. (1982) Polypeptide spectrum of hepatocyte subcellular structures isolated from intact and clofibrate-treated rats. Voprosy Meditsinskoi Khimii (in Russian) 1, 7177.
Beno, I., Volkovova, K., Staruchova, M. and Koszeghyova, L. (1994) The activity of Cu/Zn-superoxide dismutase and catalase of gastric mucosa in chronic gastritis, and the effect of alpha-tocopherol. Bratislavske Lekarske Listy 95, 914.[Medline]
Bode, C. and Bode, J. C. (1997) Alcohol's role in gastrointestinal tract. Alcohol, Health and Research World 21, 7683.
Cai, Q. and Wei, H. (1996) Effect of dietary genitisin on antioxidant enzyme activities in SENCAR mice. Nutrition and Cancer 25, 17.[ISI][Medline]
Chieco, P., Normanni, P. and Moslen, M. T. (1998) Localization of high benzaldehyde dehydrogenase activity in rat upper gastrointestinal tract mucosa: a quantitative histochemical study. Journal of Histochemistry and Cytochemistry 36, 245252.[Abstract]
Derr, R. F., Larkin, E. C. and Rao, G. A. (1988) Is malnutrition necessary for the development of alcoholic fatty liver in the rat? Medical Hypotheses 27, 277280.[ISI][Medline]
Fang, J. L. and Vaca, C. E. (1995) Development of a 32P-postlabelling method for the analysis of adducts arising through the reaction of acetaldehyde with 2'-deoxyguanosine-3'-monophosphate and DNA. Carcinogenesis 16, 21772185.[Abstract]
French, S. W., Wong, K., Jrei, L., Albano, E., Hagbjork, A. L. and Ingelman-Sundberg, M. (1993) Effect of ethanol on cytochrome P450 2E1 (CYP2E1), lipid peroxidation, and serum protein adduct formation in relation to liver pathology pathogenesis. Experimental and Molecular Pathology 58, 175.[ISI][Medline]
Hakkak, R., Korourian, S., Ronis, M. J., Ingelman-Sundberg, M. and Badger, T. M. (1996) Effect of diet and ethanol on the expression and localization of cytochromes P450 2E1 and P450 2C7 in the colon of male rats. Biochemical Pharmacology 51, 6169.[ISI][Medline]
Homann, N., Karkkainen, P., Koivisto, T., Nosova, T., Jokelainen, K. and Salaspuro, M. (1997) Effect of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal mucosa. Journal of the National Cancer Institute 89, 16561657.
Jokelainen, K., Siitonen, A., Jousimies-Somer, H., Nosova, T., Heine, R. and Salaspuro, M. (1996) In vitro alcohol dehydrogenase-mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man. Alcoholism: Clinical and Experimental Research 20, 967972.[ISI][Medline]
Jokelainen, K., Nosova, T., Koivisto, T., Vakevainen, S., Jousimies-Somer, H., Heine, R. and Salaspuro, M. (1997) Inhibition of bacteriocolonic pathway for ethanol oxidation by ciprofloxacin in rats. Life Sciences 61, 17551762.[ISI][Medline]
Julkunen, R. J. K., DiPadova, C. and Lieber, C. S. (1985) First pass metabolism of ethanol: a gastrointestinal barrier against the systemic toxicity of ethanol. Life Sciences 37, 567573.[ISI][Medline]
Koivisto, T. and Salaspuro, M. (1996) Aldehyde dehydrogenase of the rat colon: comparison with other tissues of the alimentary tract and the liver. Alcoholism: Clinical and Experimental Research 20, 551555.[ISI][Medline]
Korourian, S., Hakkak, R., Ronis, M. J., Shelnutt, S. R., Waldron, J., Ingelman-Sundberg, M. and Badger, T. M. (1999) Diet and risk of ethanol-induced hepatotoxicity: carbohydrate-fat relationships in rats. Toxicological Sciences 47, 110117.[Abstract]
Kune, G. A. and Vitetta, L. (1992) Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. Nutrition and Cancer 18, 97111.[ISI][Medline]
Lamboeuf, Y., de Saint Blanquat, G. and Derache, R. (1981) Mucosal alcohol dehydrogenase- and aldehyde dehydrogenase-mediated ethanol oxidation in the digestive tract of the rat. Biochemical Pharmacology 30, 542545.[ISI][Medline]
Lieber, C. S. (1997) Gastric ethanol metabolism and gastritis: interactions with other drugs, Helicobacter pylori, and antibiotic therapy (19571997) a review. Alcoholism: Clinical and Experimental Research 21, 13601366.[ISI][Medline]
Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randal, R. J. (1951) Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry 193, 265275.
Maier, H., Sennewald, E., Heller, G. F. and Weidauer, H. (1994a) Chronic alcohol consumption the key risk factor for pharingeal cancer. Otolaringology and Head and Neck Surgery 110, 168173.
Maier, H., Weidauer, H., Zoller, J., Seitz, H. K., Flentje, M., Mall, G. and Born, I. A. (1994b) Effect of chronic alcohol consumption on the morphology of the oral mucosa. Alcoholism: Clinical and Experimental Research 18, 387391.[ISI][Medline]
Mezey, E. and Potter, J. J. (1983) Separation and partial characterization of multiple forms of rat liver alcohol dehydrogenase. Archives of Biochemistry and Biophysics 225, 787794.[ISI][Medline]
Pietruszko, R. (1979) Nonenthanol substrates of alcohol dehydrogenase. In Biochemistry and Pharmacology of Ethanol, Vol. 1, Majchrowicz, E. and Noble, E. P. eds, pp. 87106. Plenum Press, New York.
Pronko, P. S., Kuzmich, A. B. and Zimatkin, S. M. (1993) Acetaldehyde concentration in the blood of intact rats after chronic alcohol administration and effect of aldehyde dehydrogenase inhibitors. Voprosy Narcologii No. 3, 4042 (in Russian).
Salaspuro, M. (1997) Microbial metabolism of ethanol and acetaldehyde and clinical consequences. Addiction Biology 2, 3546.[ISI]
Salmela, K. S., Kaihovaara, P., Salaspuro, M. and Roine, R. P. (1996) Role of catalase in rat gastric mucosal ethanol metabolism in vitro. Alcoholism: Clinical and Experimental Research 20, 10111015.[ISI][Medline]
Salmela, K. S., Sillanaukee, P., Itala, L., Vakevainen, S., Salaspuro, M. and Roine, R. P. (1997) Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation. Journal of Laboratory and Clinical Medicine 129, 627633.[ISI][Medline]
Seitz, H. K. and Oneta, C. M. (1998) Gastrointestinal alcohol dehydrogenase. Nutrition Reviews 56, 5260.[ISI][Medline]
Seitz, H. K. and Pöschl, G. (1997) The role of gastrointestinal factors in alcohol metabolism. Alcohol and Alcoholism 32, 543549.[Abstract]
Seitz, H. K., Korsten, M. A. and Lieber, C. S. (1979) Ethanol oxidation by intestinal microsomes: increased activity after chronic ethanol administration. Life Sciences 25, 14431448.[ISI][Medline]
Seitz, H. K., Bosche, J., Czygan, P., Veith, S. and Kommerell, B. (1982) Microsomal ethanol oxidation in the colonic mucosa of the rat. Effect of chronic ethanol ingestion. Naunyn-Schmiedeberg's Archives of Pharmacology 320, 8184.[ISI][Medline]
Seitz, H. K., Simanowski, U. A., Garzon, F. T., Rideout, J. M., Peters, T. J., Koch, A., Berger, M. R., Einecke, H. and Maiwald, M. (1990) Possible role of acetaldehyde in ethanol-related cocarcinogenesis in the rat. Gastroenterology 98, 406413.[ISI][Medline]
Seitz, H. K., Egerer, G., Oneta, C., Kramer, S., Sieg, A., Klee, F. and Simanowski, U. A. (1996) Alcohol dehydrogenase in the human colon and rectum. Digestion 57, 105108.[ISI][Medline]
Seitz, H. K., Poschl, G. and Simanowski, U. A. (1998) Alcohol and cancer. Recent Developments in Alcoholism 14, 6795.[Medline]
Shimizu, M., Lasher, J. M., Tsutsumi, M. and Lieber, C. S. (1990) Immunohistochemical localization of ethanol inducible cytochrome P450 2E1 in rat alimentary tract. Gastroenterology 99, 10441050.[ISI][Medline]
Simanowski, U. A., Suter, P., Stickel, F., Maier, H., Waldherr, R., Smith, D., Russell, R. M. and Seitz, H. K. (1993) Esophageal epithelial hyperproliferation following long-term alcohol consumption in rats: effect of age and salivary gland function. Journal of the National Cancer Institute 85, 20302033.[ISI][Medline]
Simanovski, U. A., Suter, P., Russel, R. M., Heller, M., Waldherr, R., Ward, R., Peters, T. J., Smith, D. and Seitz, H. K. (1994) Enhancement of ethanol induced rectal mucosal hyperregeneration with the age in F344 rats. Gut 35, 11021106.[Abstract]
Simanowski, U. A., Homann, N., Knuhl, M., Arce, L., Waldherr, R., Conradt, C., Bosch, F. X. and Seitz, H. K. (2001) Increased rectal cell proliferation following alcohol abuse. Gut 49, 418422.
Stohs, S. J., Grafstrom, R. C., Burke, M. D., Moldeus, P. W. and Orrenius, S. G. (1976) The isolation of rat intestinal microsomes with stable cytochrome P-450 and their metabolism of benzo(e)pyrene. Archives of Biochemistry and Biophysics 177, 105116.[ISI][Medline]
Teschke, R., Moreno, F. and Petrides, A. S. (1981) Hepatic microsomal ethanol oxidizing system (MEDS): respective roles of ethanol and carbohydrates for the enhanced activity after chronic alcohol consumption. Biochemical Pharmacology 30, 17451751.[ISI][Medline]
Yin, C. J., Liao, C. S., Wu, C. W., Li, T. T., Chen, L. L., Lai, C. L. and Tsao, T. Y. (1997) Human stomach alcohol and aldehyde dehydrogenases: comparison of expression pattern and activities in alimentary tract. Gastroenterology 112, 766775.[ISI][Medline]