Hepatotumorigenicity and Peroxisome Proliferation Induced by the Hypolipidemic CI-924 in a Two-Year Study in Male and Female B6C3F1 Mice

Toxicologic Pathology

Volumn 24, Issue 3, 1996, Pages 265-272

  Walker, Robin M ^a   Wojcinski, Zbigniew W ^a   Hofstra, Angela H ^a   King, Lena M ^a   Rogers, Joanne E ^a   Baker, Kenneth W ^a   Chang, Pil Kyu ^a   Smith, Graham S ^a  

^a Parke Davis West Africa Laboratory   (United States)

Author keywords

carcinogenicity; carnitine acetyltransferase; Cytochrome P 450; hepatic; liver; peroxisomal; ultrastructure; oxidation

Indexed keywords

5,5' [[1,1' BIPHENYL] 2,5 DIYLBIS(OXY)]BIS[2,2 DIMETHYLPENTANOIC ACID]; ANTILIPEMIC AGENT; CYTOCHROME P450; DRUG DERIVATIVE; ENZYME; GEMFIBROZIL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG CARCINOGENICITY; ENZYME ACTIVITY; FEMALE; HISTOPATHOLOGY; LIVER CANCER; LIVER CARCINOGENESIS; LONG TERM EXPOSURE; MALE; MOUSE; NONHUMAN; PEROXISOME; PRIORITY JOURNAL; ADENOMA; ANIMAL; BLOOD; CHEMICALLY INDUCED DISORDER; DISORDERS OF PEROXISOMAL FUNCTIONS; ELECTRON MICROSCOPY; LIVER; LIVER TUMOR; METABOLISM; MOUSE STRAIN; PATHOLOGY; ULTRASTRUCTURE;

ADENOMA; ANIMALS; ANTILIPEMIC AGENTS; CYTOCHROME P-450 ENZYME SYSTEM; ENZYMES; FEMALE; GEMFIBROZIL; LIVER; LIVER NEOPLASMS, EXPERIMENTAL; MALE; MICE; MICE, INBRED STRAINS; MICROSCOPY, ELECTRON; PEROXISOMAL DISORDERS;

EID: 0030010712     PISSN: 01926233     EISSN: None     Source Type: Journal    
DOI: 10.1177/019262339602400301     Document Type: Article

References (38)

1. Ashby J., Brady CR, Elcombe BM, Ishmael J., Odum J., Tugwood JD, Kettle S., and Purchase IFH (1994). Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Hum. Exp. Toxicol. 13(suppl. 2): 7-18.
2. Auwerx J. (1992). Regulation of gene expression by fatty acids and fibric acid derivatives: An integrative role for peroxisome proliferator activated receptor. Horm. Res. 38: 269-277.
3. Bendele AM, Hoover DM, van Lier RBL, Foxworthy PS, and Eacho PI (1990). Effects of chronic treatment with the leukotriene D4antagonist compound LY171883 on B6C3F1 mice. Fund. Appl. Toxicol. 15: 676-682.
4. Bieber LL, Abraham T., and Helmrath T. (1972). A rapid spectrophotometric assay for carnitine palmitoyltransferase. Anal. Biochem. 50: 509-518.
5. Budroe JD and Williams GM (1994). Antioxidant enzyme activity modulation by peroxisome proliferators. In: Peroxisome Proliferators: Unique Inducers of Drug Metabolizing Enzymes, DE Moody (ed). CRC Press, Boca Raton, Florida, pp. 137-160.
6. Cohen G., Dembiec D., and Marcus J. (1970). Measurement of catalase activity in tissue extracts. Anal. Biochem. 34: 30-38.
7. Corder CN, Kloer HU, and Price MD (1989). CI-924 effects on plasma lipids in patients with Type II and Type IV hyperlipoproteinaemia. Eur. J. Pharmacol. 37: 477-481.
8. DePierre JW, Sohlenius A-K., Eriksson AM, Soderstrom M., Permadi H., Andersson K., Sundberg C., and Lundgren B. (1994). Responses of hypoxide hydrolases, glutathione transferases, DT-diaphorase, and catalase in mouse liver to treatment with peroxisome proliferators. In: Peroxisome Proliferators: Unique Inducers of Drug Metabolizing Enzymes, DE Moody (ed). CRC Press, Boca Raton, Florida, pp. 123-136.
9. Frith CH and Ward JM (1980). A morphologic classification of proliferative and neoplastic hepatic lesions in mice. J. Environ. Pathol. Toxicol. 3: 329-351.
10. Gibson GG (1993). Peroxisome proliferators as cytochrome P450 inducers. In: Peroxisomes, G Gibson and B Lake (eds). Taylor and Francis, London, pp. 119-136.
11. Gibson GG, Diaz MJ, Chinje, and Kentish P. (1994). Induction of cytochrome P450 by peroxisome proliferators. In: Peroxisome Proliferators: Unique Inducers of Drug Metabolizing Enzymes, DE Moody (ed). CRC Press, Boca Raton, Florida, pp. 27-36.
12. Gough A., Wojcinski Z., Courtney C., McGuire E., and de la Iglesia F. (1991). Hepatocarcinogenicity of peroxisome proliferator, a phenylene(oxy)-bis 2,2-dimethylpentanoic acid, in mice but not in rats. Toxicol. Pathol. 19: 622.
13. Habig WH, Pabst MJ, and Jakoby WB (1974). Glutathione S-transferase. The first step in mercapturic acid formation. J. Biol. Chem. 249: 7130-7139.
14. Hawkins JM, Jones WE, Bonner FW, and Gibson GG (1987). The effect of peroxisome proliferators on microsomal, peroxisomal, and mitochondrial enzyme activities in the liver and kidney. Drug Me-tab. Dispos. 18: 441-515.
15. Hofstra A., King L., and Walker RM (1994). Peroxisome proliferation and P450IVA1 induction by CI-924 in B6C3F1 mice and Wistar rats. Can. J. Physiol. Pharmacol. 72(suppl. 1): 585.
16. Hofstra AH, King LM, and Walker RM (1995). Peroxisome proliferation and microsomal enzyme induction by the hypolipidemic CI-924 in rats and mice. Fund. Appl. Toxicol. 27: 277-286.
17. Kahonen MT (1976). Effect of clofibrate treatment on carnitine acetyltransferase in different subcellular fractions of rat liver. Biochem. Biophys. Acta 428: 690-701.
18. Kamath SA and Rubin E. (1972). Interaction of calcium with microsomes: A modified method for the rapid isolation of rat liver microsomes. Biochem. Biophys. Res. Commun. 49: 52-59.
19. Lake BG (1993). Role of oxidative stress and enhanced cell replication in the hepatocarcinogenicity of peroxisome proliferators. In: Peroxisomes, G Gibson and B Lake (eds). Taylor & Francis, London, pp. 595-618.
20. Lake BG (1995). Mechanisms of hepatocarcinogenicity of peroxisome-proliferating drugs and chemicals. Annu. Rev. Pharmacol. Toxicol. 35: 483-507.
21. Lazarow PB (1981). Assay of peroxisomal β-oxidation of fatty acids. Methods Enzymol. 72: 315-319.
22. Maronpot RR, Haseman JK, Boorman GA, Eustis SE, Rao GN, and Huff JE (1987). Liver lesions in B6C3F1 mice: The National Toxicology Program experience and position. Arch. Toxicol. (Suppl.) 10: 286-296.
23. Martin RA, Daly AM, DiFonzo CJ, and de la Iglesia FA (1984). Randomization of animals by computer program for toxicity studies. J. Am. Coll. Toxicol. 3: 1-11.
24. Mazel P. (1972). Comparison of microsomes from control and phenobarbital pretreated rats as to NADPH-cytochrome c reductase activity. In: Fundamentals of Drug Metabolism and Drug Disposition, BN LaDu, HG Mandel, and EL Way (eds). Williams & Wilkins, Baltimore, Maryland, pp. 575-577.
25. McGuire EJ, Fitzgerald JE, Anderson JA, Watkins JR, Andrews LK, and de la Iglesia FA (1985). Systemic toxicity evaluation of a phenylene(oxy)bis2,2-dimethylpentanoic acid, a lipid regulating agent. Toxicologist 5: 94.
26. McGuire EJ, Lucas JA, Gray RH, and de la Iglesia FA (1985). Peroxisome inducing potential of a lipid regulating agent, a phenylene(oxy)bis 2,2-dimethylpentanoic acid, in rat hepatocytes. Toxicologist 5: 156.
27. Miller GL (1959). Protein determinations for large numbers of samples. Anal. Chem. 31: 964-969.
28. Nemali MR, Reddy M., Usuda N., Reddy PG, Comeau LD, Rao MS, and Reddy JK (1989). Differential induction and regulation of peroxisomal enzymes: Predictive value of peroxisome proliferation in identifying certain nonmutagenic carcinogens. Toxicol. Appl. Pharmacol. 97: 72-87.
29. Omura T. and Sato R. (1964). The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 339: 2370-2379.
30. Paglia DE and Valentine WN (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70: 158-169.
31. Sircar I., Hoefle M., and Maxwell RE (1984). Phenelenebis(oxy)bis[2,2-dimethylpentanoic acid]s: Agents that elevate high-density lipoproteins. J. Med. Chem. 26: 1020-1027.
32. Reddy JK and Lalwani ND (1983). Carcinogenesis by hepatic peroxisome proliferators: Evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. CRC Crit. Rev. Toxicol. 12: 1-58.
33. Stott WT, Yano BL, Williams DM, Barnard SD, Hannah MA, Cieszlak FS, and Herman JR (1995). Species-dependent induction of peroxisome proliferation by haloxyfop, an aryloxyphenoxy herbicide. Fund. Appl. Toxicol. 28: 71-79.
34. Wada N., Marsman DS, and Popp JA (1992). Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication. Fund. Appl. Toxicol. 18: 149-154.
35. Ward JM (1980). Morphology of hepatocellular neoplasms in B6C3F1 mice. Cancer Lett. 9: 319-325.
36. Ward JM, Goodman DG, and Squire RA (1979). Neoplastic and nonneoplastic lesions in aging B6C3F1 mice. J. Natl. Cancer Inst. 63: 849-854.
37. Weibel ER (1979). Stereological Methods. Vol. 1. Practical Methods for Biological Morphology. Academic Press, London.
38. Yamoto T., Ohashi Y., Teranishi M., Takaoka M., Manabe S., Matsunuma N., and Makita T. (1995). Age-related changes in the susceptibility to clofibric acid, a hypolipidemic agent, of male rat liver. Toxicology 78: 141-145.