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Final Progress Reports: University of Kentucky: Activation of PCBs to Genotoxins in vivo

Superfund Research Program

Activation of PCBs to Genotoxins in vivo

Project Leader: Larry W. Robertson (University of Iowa)
Grant Number: P42ES007380
Funding Period: 1997 - 2005

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Final Progress Reports

Year:   2004  1999 

Metabolic activation of a PCB (4-chlorobiphenyl) to an initiating carcinogen was studied in rats.  In animal models PCB commercial mixtures are complete carcinogens, while in two-stage hepatocarcinogenesis both commercial PCB mixtures as well as individual congeners have activity as promoters.  Dr. Robertson’s team has recently reported that several mono- to tetra-chlorinated biphenyls have initiating activity in the livers of Fischer 344 rats.  Subsequently, they investigated the metabolic activation of one of those compounds, 4-chlorobiphenyl.  Using decreasing doses, mono-hydroxy, di-hydroxy and quinone metabolites of 4-chlorobiphenyl were evaluated for their initiating activity in Fischer 344 male rats.  Livers were evaluated for changes in morphology, and the number and volume of enzyme-altered foci (preneoplastic lesions).  Of the metabolites tested, one mono-hydroxy and one quinoid metabolite showed initiating activity.  The metabolic activation of 4-chlorobiphenyl therefore proceeds via para hydroxylation and oxidation to the ortho-(3,4)-quinone, the ultimate carcinogen.  This is the first report of the metabolic activation of a PCB to a proximate and an ultimate carcinogen.

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