Studies of early hepatocellular proliferation and peroxisomal proliferation in Wistar rats treated with herbicide diclofop

Toxicology. 2001 Feb 14;158(3):119-26. doi: 10.1016/s0300-483x(00)00371-1.

Abstract

A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight. Hepatomegaly was typically associated with proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The parallel biochemical measurements showed that there was a dose-dependent increase in peroxisomal palmitoyl-CoA oxidation and catalase activity in treated rats. Markers of hepatocellular proliferation (S- and M-phase) indicated that mitogenesis was transient and declined despite continuation of diclofop treatment. The threshold exposure level for the palmitoyl-CoA oxidation (one of the peroxisome proliferation markers) was approximately the same (14 mg/kg body weightxper day) as for the stimulation of mitogenesis in Wistar rats. However, for hepatomegaly and catalase activity the threshold exposure level was 7 mg/kg body weightxper day. The results presented here demonstrate clearly that diclofop belongs to a class of rodent PPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Catalase / analysis
  • Cell Division / drug effects
  • DNA / biosynthesis
  • Dose-Response Relationship, Drug
  • Halogenated Diphenyl Ethers
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Hepatomegaly / chemically induced
  • Herbicides / pharmacology*
  • Herbicides / toxicity
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Microscopy, Electron
  • Palmitoyl Coenzyme A / metabolism
  • Peroxisome Proliferators / pharmacology*
  • Peroxisome Proliferators / toxicity
  • Peroxisomes / drug effects
  • Peroxisomes / enzymology
  • Phenyl Ethers / pharmacology*
  • Phenyl Ethers / toxicity
  • Rats
  • Rats, Wistar
  • Thymidine / pharmacokinetics
  • Tritium

Substances

  • Halogenated Diphenyl Ethers
  • Herbicides
  • Peroxisome Proliferators
  • Phenyl Ethers
  • Tritium
  • Palmitoyl Coenzyme A
  • DNA
  • dichlorfop-methyl
  • Catalase
  • Thymidine