The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator.

Perfluorooctanoic acid (PFOA) is a peroxisome proliferator. The aim of this study was to test for its ability to act as a positive modulator of hepatocarcinogenesis, in the so-called biphasic (initiation by diethylnitrosamine 200 mg/kg ip followed by treatment with the suspected modulators) and triphasic (initiation by the same dose of diethylnitrosamine followed by a selection procedure for 2 weeks consisting of giving 2-acetylaminofluorene and in the middle of this treatment a single dose of CCl4 followed by treatment with the suspected modulators) protocols of liver carcinogenesis. In both protocols treatment with PFOA increased the incidence of malignant hepatocellular carcinoma (HCC). As compared to phenobarbital, the modulating effect of PFOA is more pronounced in a biphasic than in the triphasic protocol. In parallel with positive modulation of HCC, PFOA also selectively induced the peroxisomal acyl-CoA oxidase activity and, to a lesser extent, catalase activity.

[1]  M. Roberfroid,et al.  Phenobarbital as a promoter in the initiation/selection process of experimental rat hepatocarcinogenesis. , 1983, Carcinogenesis.

[2]  J. Vamecq,et al.  Implication of a peroxisomal enzyme in the catabolism of glutaryl-CoA. , 1984, The Biochemical journal.

[3]  G. Kennedy,et al.  Increase in mouse liver weight following feeding of ammonium perfluorooctanoate and related fluorochemicals. , 1987, Toxicology letters.

[4]  G. Williams,et al.  Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital. , 1985, Cancer research.

[5]  R. Cattley,et al.  Possible Mechanisms in Hepatocarcinogensis by the Peroxisome Proliferator Di(2-Ethylhexyl)Phthalate , 1989 .

[6]  M Tanaka,et al.  The induction of peroxisome proliferation in rat liver by perfluorinated fatty acids, metabolically inert derivatives of fatty acids. , 1985, Journal of biochemistry.

[7]  J. Warren,et al.  Phthalate esters as peroxisome proliferator carcinogens. , 1982, Environmental health perspectives.

[8]  C. Hignite,et al.  HYPOLIPIDEMIC HEPATIC PEROXISOME PROLIFERATORS FORM A NOVEL CLASS OF CHEMICAL CARCINOGENS , 1980 .

[9]  J. Reddy,et al.  DNA damage related to increased hydrogen peroxide generation by hypolipidemic drug-induced liver peroxisomes. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Lalwani,et al.  Excessive accumulation of autofluorescent lipofuscin in the liver during hepatocarcinogenesis by methyl clofenapate and other hypolipidemic peroxisome proliferators. , 1982, Cancer research.

[11]  J. Reddy,et al.  Peroxisome proliferation and lipid peroxidation in rat liver. , 1986, Cancer research.

[12]  K P Lee,et al.  Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. , 1987, Experimental and molecular pathology.

[13]  P. Baudhuin,et al.  Tissue fractionation studies. 17. Intracellular distribution of monoamine oxidase, aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase and catalase in rat-liver tissue. , 1964, The Biochemical journal.

[14]  P. Lazarow Three hypolipidemic drugs increase hepatic palmitoyl-coenzyme A oxidation in the rat. , 1977, Science.

[15]  T. Hashimoto,et al.  Induction of peroxisomal beta-oxidation enzymes in primary cultured rat hepatocytes by clofibric acid. , 1985, Journal of biochemistry.

[16]  L. C. Clark,et al.  Perfluorocarbons Having a Short Dwell Time in the Liver , 1973, Science.

[17]  R. Squire,et al.  Report of a workshop on classification of specific hepatocellular lesions in rats. , 1975, Cancer research.

[18]  Sargent Jw,et al.  Properties of perfluorinated liquids. , 1970 .

[19]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[20]  B. Lake,et al.  Effect of prolonged administration of clofibric acid and di-(2-ethylhexyl)phthalate on hepatic enzyme activities and lipid peroxidation in the rat. , 1987, Toxicology.

[21]  D. Moody,et al.  The hepatic effects of hypolipidemic drugs (clofibrate, nafenopin, tibric acid, and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. , 1978, The American journal of pathology.

[22]  G. Guilbault,et al.  New substrates for the fluorometric determination of oxidative enzymes. , 1968, Analytical chemistry.

[23]  J. Reddy,et al.  Sequential histologic study of rat liver during peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]-acetic acid (Wy-14,643)-induced carcinogenesis. , 1984, Journal of the National Cancer Institute.

[24]  Reddy Jk,et al.  Carcinogenesis by Hepatic Peroxisome Proliferators: Evaluation of the Risk of Hypolipidemic Drugs and Industrial Plasticizers to Humans , 1983 .

[25]  D. Solt,et al.  New principle for the analysis of chemical carcinogenesis , 1976, Nature.

[26]  J. Carrino,et al.  Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. A. Guenthner,et al.  Surface Active Materials from Perfluorocarboxylic and Perfluorosulfonic Acids , 1962 .

[28]  J. Reddy,et al.  Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens , 1980, Nature.

[29]  M. Rao,et al.  Absence of gamma-glutamyl transpeptidase activity in neoplastic lesions induced in the liver of male F-344 rats by di-(2-ethylhexyl)phthalate, a peroxisome proliferator. , 1987, Carcinogenesis.

[30]  M. Rao,et al.  Enhancement by Wy-14,643, a hepatic peroxisome proliferator, of diethylnitrosamine-initiated hepatic tumorigenesis in the rat. , 1978, British Journal of Cancer.