These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Evaluation of the carcinogenic potential of clofibrate in the p53+/- mouse.
    Author: Torrey CE, Campbell JA, Hoivik DJ, Miller RT, Allen JS, Mann PC, Selinger K, Rickert D, Savina PM, Santostefano MJ.
    Journal: Int J Toxicol; 2005; 24(5):289-99. PubMed ID: 16257849.
    Abstract:
    This study was conducted as part of International Life Sciences Institute (ILSI) program to evaluate the carcinogenic potential of clofibrate, a nongenotoxic, peroxisome proliferator-activated receptor (PPAR) alpha agonist, following oral administration to p53+/- heterozygous mice for a minimum of 26 weeks. p-Cresidine, a urinary bladder carcinogen, was given orally at 400 mg/kg/day as a positive control. Initial clofibrate doses were 50, 250, and 400 mg/kg/day for males and 50, 200, and 500 mg/kg/day for females. Due to unexpected mortality during the first week of dosing, clofibrate doses were lowered to 25, 75, and 100 mg/kg/day for males and 25, 75, and 125 mg/kg/day for females. Clinical signs and mortality were greater in p53+/- than wild-type (WT) mice. With the exception of liver weights, no marked differences in any other parameters either between the sexes or between WT and p53+/- mice were noted. Moderate increases in liver weights noted in WT males given 100 mg/kg/day clofibrate were not associated with any microscopic changes. No neoplastic response was observed in p53+/- mice after 6 months of exposure to clofibrate at doses up to 100 mg/kg/day for males and 125 mg/kg/day for females. Transitional-cell hyperplasia and carcinoma of the urinary bladder were noted in both sexes given p-cresidine, demonstrating that the p53+/- mouse responded to a known mouse carcinogen as expected. Clofibrate produced non-neoplastic findings in the adrenals, pancreas, and prostate, whereas p-cresidine affected the kidney, liver, pancreas, and spleen.
    [Abstract] [Full Text] [Related] [New Search]