In-vitro hepatotoxicity of three dichlorobenzene isomers in human liver slices

Hum Exp Toxicol. 1991 Sep;10(5):357-63. doi: 10.1177/096032719101000510.

Abstract

1 The cytotoxicity of dichlorobenzenes in cultured rat liver slices has previously been shown to be strain specific and biotransformation related. 2 In order to extrapolate animal models to humans, the dichlorobenzenes were incubated with human liver slices to try to clarify their hepatotoxic potential in man. 3 The degree of hepatotoxicity observed with the dichlorobenzenes depended on whether Waymouth's or Krebs-Henseleit was used as the incubation medium. 4 All three dichlorobenzenes (1 mM) produced no significant differences from control when incubated in Waymouth's medium. However, in the Krebs-Henseleit buffer there was a substantial increase in cytotoxicity. 5 In both incubation mediums the dichlorobenzene isomers exhibited the following rank order 1,3-DCB greater than 1,2-DCB greater than 1,4-DCB. 6 1,2-dichlorobenzene hepatotoxicity was blocked by metyrapone, 1,3-dichlorobenzene toxicity was blocked by SKF 525-A and neither one of these inhibitors could block the 1,4-dichlorobenzene cytotoxicity. 7 The use of human liver tissues to evaluate potential toxicants merits consideration since the hepatotoxicity of xenobiotics and drugs in man is the ultimate question.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chlorobenzenes / toxicity*
  • Female
  • Humans
  • In Vitro Techniques
  • Liver / drug effects*
  • Male
  • Metyrapone / pharmacology
  • Middle Aged
  • Proadifen / pharmacology

Substances

  • Chlorobenzenes
  • 2-dichlorobenzene
  • 1,3-dichlorobenzene
  • Proadifen
  • 4-dichlorobenzene
  • Metyrapone