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.
Fisher
R
R
University of Arizona, Department of Pharmacology, Tucson 85724.
Barr
J
J
Zukoski
C F
CF
Putnam
C W
CW
Sipes
I G
IG
Gandolfi
A J
AJ
Brendel
K
K
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