Elsevier

Biochemical Pharmacology

Volume 34, Issue 22, 15 November 1985, Pages 4051-4057
Biochemical Pharmacology

Studies on the distribution and co valent binding of 1,1-dichloroethylene in the mouse: Effect of various pretreatments on covalent binding in vivo

https://doi.org/10.1016/0006-2952(85)90386-7Get rights and content

Abstract

The distribution and covalent binding of a single dose of [1, 2-14C]1, 1-dichloroethylene (DCE; 125 mg/kg, i.p.) was studied in male C57B1/6N mice. Total radioactivity was distributed in whole homogenates of all tissues studied, with peak levels occurring within 6 hr. Covalent binding of radioactive material peaked at 6–12 hr in all tissues, and highest levels were found in kidney, liver, and lung with smaller amounts in skeletal muscle, heart, spleen, and gut. Covalent binding in kidney, liver, and lung fell to 50% of peak levels in about 4 days. Between 12 hr and 4 days after DCE administration, 70–100% of total radioactivity present in homogenates of kidney, liver, and lung was covalently bound. The three tissues showed a similar spread in total radioactivity in subcellular fractions 24 hr after exposure to DCE; most of the radioactivity was covalently bound (60–100%) and distributed fairly uniformly with a slight tendency to concentrate in the mitochondrial fraction. Phenobarbital (PB) and 3-methylcholanthrene (3-MC) pretreatments increased the covalent binding in the liver and lung but had no effect in the kidney. Piperonyl butoxide and SKF-525A decreased the covalent binding in liver and lung, but the latter increased binding in the kidney while the former decreased it. Diethylmaleate administration increased the covalent binding (2- to 3-fold) in all three tissues as well as increasing lethal toxicity. These results are consistent with the view that DCE is metabolized to some reactive intermediate(s) which may be detoxified by conjugation with glutathione

References (41)

  • L.J. Jenkins et al.

    Toxic. appl. Pharmac.

    (1972)
  • M.E. Andersen et al.

    Toxic, appl. Pharmac.

    (1979)
  • L.J. Jenkins et al.

    Toxic. appl. Pharmac.

    (1978)
  • K.R. Krijgsheld et al.

    Toxic. appl. Pharmac.

    (1984)
  • K.R. Krijgsheld et al.

    Biochem. Pharmac.

    (1984)
  • Y. Masuda et al.

    Toxic. appl. Pharmac.

    (1983)
  • R.J. Jaeger et al.

    Expl molec. Path.

    (1974)
  • M.E. Andersen et al.

    Toxic. appl. Pharmac.

    (1980)
  • M.J. McKenna et al.

    Toxic. appl. Pharmac.

    (1978)
  • O.H. Lowry et al.

    J. biol. Chem.

    (1951)
  • A.K. Costa et al.

    Biochem. Pharmac.

    (1982)
  • A. Poland et al.

    J. biol. Chem.

    (1976)
  • B.D. Hammock et al.

    Toxic. appl. Pharmac.

    (1983)
  • M.G. Ott et al.

    J. occup. Med.

    (1976)
  • M. Deinzer et al.

    Environ. Hlth Perspect.

    (1978)
  • H. Grein et al.

    Biochem. Pharmac.

    (1975)
  • H. Bartsch et al.

    Archs Toxic.

    (1979)
  • C. Maltoni et al.

    Medna Lav.

    (1977)
  • C.C. Lee et al.

    J. Toxic environ. Hlth

    (1978)
  • E.S. Reynolds et al.

    Am. J. Path.

    (1975)
  • Cited by (26)

    • Halogenated Hydrocarbons

      2010, Comprehensive Toxicology, Second Edition
    View all citing articles on Scopus
    View full text