In-vitro hepatotoxicity of three dichlorobenzene isomers in human liver slices.
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.
University of Arizona, Department of Pharmacology, Tucson 85724.
R
R
Fisher
J
J
Barr
C F
CF
Zukoski
C W
CW
Putnam
I G
IG
Sipes
A J
AJ
Gandolfi
K
K
Brendel
D000293:Adolescent; D000328:Adult; D000368:Aged; D002722:Chlorobenzenes / Q000633:toxicity*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008875:Middle Aged; D011335:Proadifen / Q000494:pharmacology
D002722:Chlorobenzenes; C004726:2-dichlorobenzene; C042146:1,3-dichlorobenzene; D011335:Proadifen; C018511:4-dichlorobenzene; D008797:Metyrapone