Abstract
Compared to controls receiving physiological saline, the i.p. administration of dimethylnitrosamine (DMN) on 5 consecutive days to rats fed a nutritionally adequate liquid diet resulted 24 hours after the last injection in significant increases of glutamic dehydrogenase (GDH), glutamic oxylacetate transaminase (GOT), and glutamic pyruvate transaminase (GPT) activities in the serum, indicating a striking hepatotoxic effect of this compound. This was confirmed by the histological demonstration of massive centrolobular necrosis. Conversely, following pretreatment of the rats with an ethanol containing liquid diet for 23 days and subsequent administration of DMN the increases of serum enzyme activities and massive centrolobular necrosis could not be observed. These results therefore suggest that chronic alcohol consumption protects from hepatotoxicity due to DMN, most probably due to an enhancement of detoxifying pathways of the parent component or one of its toxic metabolites.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Bergmeyer, H.U. and Bernt, E. (1974) in: Methoden der enzymatischen Analyse. Verlag Chemie, Weinheim.
Cottrell, R.C., Lake, B.G., Phillips, J.C. and Gangolli, S.D. (1977) The hepatic metabolism of 15N labelled dimethylnitrosamine in the rat. Biochem. Pharmacol. 26: 809.
Czygan, P., Greim, H., Garro, A.J., Hutterer, F., Schaffner, F., Popper, H., Rosenthal, O. and Cooper, D.Y. (1973) Microsomal metabolism of dimethylnitrosamine and the cytochrome P-450 dependency of its activation to a mutagen. Canc. Res. 33: 2983.
DeCarli, L.M. and Lieber, C.S. (1967) Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet. J. Nutr. 91: 331.
Hasumura, Y., Teschke, R. and Lieber, C.S. (1974) Increased carbon tetrachloride hepatotoxicity and its mechanism, after chronic ethanol consumption. Gastroenterology 66: 415.
Iseri, O.A., Lieber, C.S. and Gottlieb, L.S. (1966) The ultra-structure of fatty liver induced by prolonged ethanol ingestion. Amer. J. Path. 48: 535.
Joly, J.G., Ishii, H., Teschke, R., Hasumura, Y. and Lieber, C.S. (1973) Effect of chronic ethanol feeding on the activities and submicrosomal distribution of reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase and the demethylase for aminopyrine and ethylmorphine. Biochem. Pharmacol. 22: 1532.
Kroeger-Koepke, M.B. and Michejda, C.J. (1979) Evidence for several demethylase enzymes in the oxidation of dimethylnitrosamine and phenylmethylnitrosamine by rat liver fractions. Canc. Res. 39: 1587.
Kunz, W., Schaude, R. and Thomas, C. (1969) Die Beeinflussung der Nitrosamincarcinogenese durch Phenobarbital and Halogenkohlenwasserstoffe. Z. Krebsforsch. 72: 291.
Lake, B.G., Cottrell, R.C., Phillips, J.C., Gangolli, S.D. and Lloyd, A.G. (1977) Further studies on the metabolism of dimethylnitrosamine by rat liver in vitro..Biochem. Soc. Transact. 5: 1013.
Lieber, C.S. and DeCarli, L.M. (1970) Hepatic microsomal ethanol oxidizing system: In vitro characteristics and adaptive properties in vivo. J. Biol. Chem. 245: 2505.
Lotlikar, P.D., Baldy, W.J., Jr.. and Dwyer, E.N. (1975) Dimethylnitrosamine demethylation by reconstituted liver microsomal cytochrome P-450 enzyme system. Biochem. J. 152: 705.
Nayak, N.C., Chopra, P., Dhar, A. and Das, P.K. (1975) Diverse mechanisms of hepatocellular injuries due to chemicals: Evidence in rats administered carbon tetrachloride or dimethylnitrosamine. Br. J. Exp. Path. 56:103.,
Phillips, J.C., Topp, C.E., Mendis, D., Walker, R. and Gangolli, S.D. (1978) The effect of ethoxyquine on the hepatotoxicity of dimethylnitrosamine and carbon tetrachloride in the rat. Biochem. Soc. Transact. 6: 1244.
Rubin, E., Hutterer, F. and Lieber, C.S. (1968) Ethanol increases hepatic smooth endoplasmic reticulum and drug-metabolizing enzymes. Science 159: 1469.
Schmähl, D.,- Thomas, C., Sattler, W. and Scheid, G.F. (1965) Experimentelle Untersuchungen zur Syncarcinogenese. Z. Krebsforsch. 66: 526.
Seitz, A., Garro, J. and Lieber, C.S. (1979) Increased activation of procarcinogens after ethanol. Fed. Proc. 38: A6204.
Teschke, R., Hasumura, Y., Joly, J.G., Ishii, H. and Lieber, C.S. (1972) Microsomal ethanol oxidizing system ( MEOS ): Purification and properties of a rat liver system free of catalase and alcohol dehydrogenase. Biochem. Biophys. Res. Comm. 49: 1187.
Teschke, R., Matsuzaki, S., Ohnishi, K., Hasumura, Y. and Lieber, C.S. (1977a) Metabolism of alcohol at high concentrations: role and biochemical nature of hepatic microsomal ethanol oxidizing system, in: Advances in Experimental Medicine and Biology, 85a, p. 252, M.M. Gross, ed., Plenum Press, New York.
Teschke, R., Matsuzaki, S., Ohnishi, K., DeCarli, L.M. and Lieber, C.S. (1977b) Microsomal ethanol oxidizing system (MEOS): Current status of its characterization and its role. Alcoholism, 1: 7.
Teschke, R., Rauen, J., Gellert, J, Stutz, G. and Strohmeyer, G. (1978) Klinik alkoholbedingter Leberschäden. Leber Magen Darm, 8: 291.
Teschke, R., Stutz, G. and Strohmeyer, G. (1978) Increased drug induced hepatotoxicity after chronic alcohol consumption. Proceedings of the 6th World Congress of Gastroenterology, Madrid, p. 93.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1980 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gellert, J. et al. (1980). Decreased Hepatotoxicity of Dimethylnitrosamine (DMN) Following Chronic Alcohol Consumption. In: Thurman, R.G. (eds) Alcohol and Aldehyde Metabolizing Systems-IV. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1419-7_25
Download citation
DOI: https://doi.org/10.1007/978-1-4757-1419-7_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-1421-0
Online ISBN: 978-1-4757-1419-7
eBook Packages: Springer Book Archive