Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene: Possible relevance to species differences in hepatocarcinogenicity

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Abstract

Trichloroethylene (TRI), administered by gavage for 10 consecutive days, at doses of 500 to 1500 mg/kg body wt increased liver weight (175% of control), decreased hepatic DNA concentration (66% of control), and increased the synthesis of DNA (500% of control; as measured by [3H]dT incorporation) in B6C3F1 mice and Alderley Park mice. Similar treatment of Osborne-Mendel rats or Alderley Park rats resulted in smaller increases in liver weight (130% of control) and decreases in DNA concentration (83% of control). No effect of TRI on DNA synthesis was seen in rats. The increased DNA synthesis in the mouse was not apparently due to regenerative hyperplasia since no signs of necrosis were seen. Furthermore the increased [3H]dT incorporation probably represented semiconservative replication of DNA and not repair, since a parallel increase of mitotic figures was observed. Hence, the liver growth noted after TRI administration appears to be due to liver cell enlargement (hypertrophy) in the rat, but both hypertrophy and hyperplasia (cell proliferation) in the mouse. An important observation has been that TRI induced the peroxisomal enzyme activities, catalase, and cyanide-insensitive palmitoyl-CoA oxidation (147 and 786% of control, respectively), in mice but not in rats. Furthermore, increases in peroxisome volume density (up to 1110% of control) were observed in mice receiving TRI. These observations lead us to suggest that the species difference in hepatocarcinogenicity of TRI, seen between the rat and mouse, is possibly due to a species difference in peroxisome proliferation and cell proliferation, the peroxisome proliferation leading to increased reactive oxygen species and DNA damage, and the cell proliferation then acting to promote this lesion.

References (50)

  • A.M. Schumann et al.

    The pharmacolinetics and macromolecular interactions of perchloroethylene in mice and rats as related to oncogenicity

    Toxicol. Appl. Pharmacol

    (1980)
  • H.F. Stich et al.

    The need for a mammalian test system for mutagens: Action of some reducing agents

    Cancer Letts

    (1978)
  • W.T. Stott et al.

    The pharmacokinetics and macromolecular interactions of trichloroethylene in mice and rats

    Toxicol. Appl. Pharmacol

    (1982)
  • L. Waskell

    A study of the mutagenicity of anaesthetics and their metabolites

    Mutal. Res

    (1978)
  • O. Axelson et al.

    A cohort study on trichloroethylene exposure and cancer mortality

    J. Occup. Med

    (1978)
  • S. Banerjee et al.

    Covalent binding of the carcinogen trichloroethylene to hepatic microsomal proteins and to exogenous DNA in vitro

    Cancer Res

    (1978)
  • H. Bartsch et al.

    Mutagenic and alkylating metabolites of haloethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver tissues

    Arch. Toxicol

    (1979)
  • H.M. Bolt et al.

    Incubation of 14C-trichloroethylene vapour with rat liver microsomes: Uptake of radioactivity and covalent protein binding of metabolites

    Int. Arch. Occup. Environ. Health

    (1977)
  • H.M. Bolt et al.

    Irreversible binding of chlorinated ethylene to macromolecules

    Environ. Health Perspect

    (1977)
  • G. Bronzetti et al.

    Genetic activity of trichloroethylene in yeast

    J. Environ. Pathol. Toxicol

    (1978)
  • C. Bruni et al.

    The fine structure of the parenchymal cell of the normal rat liver. 1. General Observations

    Amer. J. Pathol

    (1965)
  • W.J. Bruyninckx et al.

    Are physiological oxygen concentrations mutagenic?

    Nature (London)

    (1978)
  • K. Burton

    A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid

    Biochem. J

    (1956)
  • Committee of Principal Investigators

    WHO cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: Mortality follow up

    Lancet

    (1980)
  • R.M. Elashoff et al.

    Comparison and evaluation of some experimental designs for use in carcinogen screening

    J. Natl. Cancer Inst

    (1979)
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    1

    Present address: Corporate Bioscience Group, ICI PLC, The Heath, Runcorn, Cheshire, U.K.

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    Present address: Department of Pharmacology, University College, Foster Avenue, Blackrock, Dublin, Ireland.

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