Occurrence of Two Different Types of Glutathione S-Transferase Placental Form-Positive Hepatocytes after a Single Administration of 2,3,7,8-Tetrabromodibenzo-p-dioxin in Rats

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Occurrence of glutathione S-transferase placental form (GST-P)-positive hepatocytes was examined, using 15 Wistar rats of both sexes each orally administered 2,3,7,8-tetrabromo-dibenzo-p-dioxin (TBDD) by gavage at a single dose of 0, 10, 30, 100 or 300 μg/kg body weight. Liver tissues were stained with anti-GST-P antibody. Two different types of GST-P-positive hepatocytes were found in the TBDD-dosed rat. One type was of the hepatocytes stained homogeneously with anti-GST-P antibody and clearly distinguishable from the surrounding normal tissue. The foci were composed of 2 to 60 hepatocytes exhibiting morphologically focal and clonal proliferation. The GST-P-positive hepatocellular foci occurred at two higher dose levels and only on Day 36 after the single administration. Another type was of the area occupied by the positively but heterogeneously stained hepatocytes appearing predominantly in the centrilobular region, at lower dose levels and persistently on Day 2 through 36. The stained hepatocytes appeared to be neither focally nor clonally proliferating. Females were more susceptible to formation of the two differently stained hepatocytes than males. It is suggested that the GST-P-positive foci represent an early stage of hepatocarcinogenesis, while the GST-P-positive area is associated with the induction of detoxifying Phase II GSTs.
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