This study evaluates and quantifies the interactive hepatic
tumor promoting effects of two
PCBs, the
Ah receptor agonist
PCB 126 (3,3',4,4',5-pentachlorobiphenyl) and the
constitutive androstane receptor (CAR) agonist
PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl). Promotion of altered hepatic foci was evaluated utilizing a medium-term 8-week bioassay for promoters of hepatocarcinogenesis. The assay employs placental
glutathione-S-transferase positive (GST-P+) liver cell foci as markers of preneoplasia in female Fischer 344 rats treated with the known initiator
diethylnitrosamine followed by partial
hepatectomy and by gavage exposure to test chemicals. GST-P+ foci were quantified by histomorphometry and were reported as areas and numbers of GST-P+ foci within the area of liver examined. For
PCB 126, the doses were 0.1, 1.0, and 10 microg/kg
body weight. For
PCB 153, the doses were 10, 100, 1000, 5000, and 10,000 microg/kg
body weight. Combined
PCB 126 and 153 exposures were 0.1 + 10, 1 + 100, 10 + 1000, 10 + 5000, and 10 + 10,000 microg/kg, respectively. Individual PCB treatment resulted in dose dependent increases in liver and adipose concentrations. Hepatic
PCB 153 levels were significantly increased (p < 0.01) after combined exposure. Treatment with
PCB 126 or
PCB 153 alone resulted in a significant (p < 0.01) dose dependent increase in GST-P+ foci area and number compared with controls. Treatment with the mixture of
PCB 126 and 153 resulted in antagonistic GST-P+ focus formation (p < 0.001) for both foci area and number. The less than additive effect was present at all 5
PCB 126/
PCB 153 dose combinations, including the low doses of
PCB 126 and 153 that did not show significant promotional activity alone.