Acute and reversible fatty metamorphosis of cultured rat hepatocytes

Rat hepatocyte cell line M6 B347 and J525, among which only M6 is slightly deviated from diploidy, showed marked microvesicular fatty metamorphosls in response to treatment with Tweens at concentratlons of 0.05–0.025% In Eagle's minimum essentlal medium (MEY). Within 24h treated cells became fatty at 100% In frequency and filled with small lipld droplets, as revealed by fat stalning or at the ultrastructural level. Fatty hepatocytes, however, took again non‐fatty morphology 72 h after withdrawal of Tweens from the culture medium. Growth of the cell exhibited mlld retardation at the early phase of the treatment but almost simllar cell density to that of control cells was achleved 24 h after the treatment. Other detergents without fatty‐acld moiety, including NP‐40, triton X‐100, sodium deoxychollc acld and sodium cholic acld, were ineffective to induce fatty change. Oleate, a fatty‐acld molety of Tween 80 or 85, and linolate caused reversible fatty metarnorphosls of the cell llnes at concentratlons of 1.9X10‐4 mol/L or more and 3.8X10‐‐4 mol/L or more, respectively. Ethanol Induced mild steatosls of the cell lines and enhanced fatty change by linolate. Hepatic fatty acid‐binding proteln was not detected in the cell lines before or after the Induction of fatty change. These results Indicate that fatty acid Itself Is directiy Incorporated In cultured rat hepatocytes and expelled 3 days later without apparent cell degeneration.

[1]  A. J. Corbett,et al.  Reye syndrome associated with aspirin therapy for systemic lupus erythematosus. , 1985, Pediatrics.

[2]  M. Tisdale,et al.  Effect of polyunsaturated fatty acids on the growth of murine colon adenocarcinomas in vitro and in vivo. , 1994, British Journal of Cancer.

[3]  W. Schubert,et al.  Cholesterol ester storage disease and mesenteric lipodystrophy. , 1984, American journal of clinical pathology.

[4]  J. Prieto,et al.  Fatty Liver Disease and Nutritional Liver Damage , 1992 .

[5]  G. Farrell,et al.  Human cytochrome P450 isoforms , 1990 .

[6]  A. Glasgow,et al.  Production of the Features of Reye's Syndrome in Rats with 4-Pentenoic Acid , 1975, Pediatric Research.

[7]  K. Breen,et al.  Idiopathic acute fatty liver of pregnancy , 1970, Gut.

[8]  D F Horrobin,et al.  Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. , 1986, Journal of the National Cancer Institute.

[9]  K. Ishak,et al.  Cryptogenic acute cholangitis--association with toxic shock syndrome. , 1981, American journal of clinical pathology.

[10]  R. Peters,et al.  Tetracycline-induced fatty liver in nonpregnant patients. A report of six cases. , 1967, American journal of surgery.

[11]  Meenakshi Singh,et al.  Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat. , 1994, Cancer research.

[12]  M. Heimberg,et al.  Hepatic lipid metabolism in experimental diabetes. V. The effect of concentration of oleate on metabolism of triglycerides and on ketogenesis. , 1969, The Journal of biological chemistry.

[13]  M. J. Newman Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Zermansky Ag Letter: Chronic sinusitis. , 1974, Lancet.

[15]  N. Ryan,et al.  AFLATOXIN B1 AND REYE'S SYNDROME , 1978, The Lancet.

[16]  D. Horrobin,et al.  Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation. , 1988, Journal of the National Cancer Institute.

[17]  W. Arnold,et al.  Chronic camphor ingestion mimicking Reye's syndrome. , 1983, Gastroenterology.

[18]  R. Tiwari,et al.  Modulation of gene expression by selected fatty acids in human breast cancer cells. , 1991, Anticancer research.

[19]  D. Rose,et al.  Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. , 1991, Journal of the National Cancer Institute.

[20]  K. Ishak New developments in diagnostic liver pathology. , 1987, Monographs in pathology.

[21]  R. Ellefson,et al.  An aflatoxin in the liver of a patient with Reye-Johnson syndrome. , 1976, Mayo Clinic proceedings.

[22]  A. J. Mcadams,et al.  The hepatic lesion in Reye's syndrome. , 1975, Gastroenterology.

[23]  F. Mullick,et al.  HEPATIC AND CEREBRAL PATHOLOGY FINDINGS IN CHILDREN WITH FATAL SALICYLATE INTOXICATION: FURTHER EVIDENCE FOR A CAUSAL RELATION BETWEEN SALICYLATE AND REYE'S SYNDROME , 1983, The Lancet.

[24]  K. Ishak,et al.  The liver in fatal exertional heatstroke. , 2008, Liver.

[25]  D. Sinniah,et al.  MARGOSA OIL POISONING AS A CAUSE OF REYE'S SYNDROME , 1981, The Lancet.

[26]  K. Fearon,et al.  Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines. , 1994, British Journal of Cancer.

[27]  D. Rose,et al.  Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. , 1994, Cancer research.

[28]  H. Zimmerman Hepatic injury due to drugs and toxin , 1994 .

[29]  P. Engel,et al.  Defects of metabolism of fatty acids in the sudden infant death syndrome. , 1985, British medical journal.

[30]  T. Kishimoto,et al.  Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins. , 1994, Cancer research.

[31]  J. Sato,et al.  Isozyme patterns of branched-chain amino acid transaminase in cultured rat hepatocytes. , 1973, Cancer research.

[32]  J. Naggert,et al.  Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. Hendriksen,et al.  Reye's syndrome associated with long-term aspirin therapy. , 1984, JAMA.

[34]  H. Nakabayashi,et al.  Long-term cultivation of two diploid epithelial cell lines derived from normal rat liver cells. , 1974, Acta medica Okayama.

[35]  R. Peters,et al.  Alcoholic foamy degeneration ― a pattern of acute alcoholic injury of the liver , 1983 .

[36]  K. Ishak,et al.  Valproate‐Induced Hepatic Injury: Analyses of 23 Fatal Cases , 2007, Hepatology.

[37]  B. Combes,et al.  Tetracycline and the liver. , 1972, Progress in liver diseases.

[38]  K. Ishak,et al.  Acute fatty liver of pregnancy: A clinicopathologic study of 35 cases , 1985, Hepatology.

[39]  D. Horrobin,et al.  Lipid peroxidation in human breast cancer cells in response to gamma-linolenic acid and iron. , 1992, Anticancer research.

[40]  D. Sinniah,et al.  レイエ症候群の原因としてのせんだん油(margosa oil)中毒 , 1981 .

[41]  R. Sinniah,et al.  Animal model of margosa oil ingestion with Reye‐like syndrome. Pathogenesis of microvesicular fatty liver , 1989, The Journal of pathology.

[42]  R. Weesner,et al.  Lipogranulomas in non-fatty human livers. A mineral oil induced environmental disease. , 1982, American journal of clinical pathology.

[43]  S. Sabesin,et al.  Accumulation of nascent lipoproteins in rat hepatic golgi during induction of fatty liver by orotic acid. , 1977, Laboratory investigation; a journal of technical methods and pathology.

[44]  Toshimitsu Suzuki,et al.  Distribution of Type I Collagen and Basement Membrane Proteins in the Cultures of Cloned Epithelial Liver Cells , 1982 .