Acute exposure to hepatotoxic doses of 2,3,7,8-tetrachloro-
dibenzo-p-dioxin (
TCDD) in mice is characterized by differential gene expression that can be phenotypically anchored to elevated levels of serum
alanine aminotransferase, increased relative liver weights, hepatic steatosis,
inflammation, and hepatocellular
necrosis. Unlike most studies that focus on acute exposure effects, this study evaluated the long-term effects of a single oral gavage of 30 μg/kg
TCDD at 1, 4, 12, 24, 36, and 72 weeks postdose in ovariectomized C57BL/6 mice. Hepatic
TCDD levels were almost completely eliminated by 24 weeks with a calculated half-life of 12 days. Hepatic gene expression analysis identified 395 unique differentially expressed genes between 1 and 12 weeks that decreased to ≤ 8 by 72 weeks, consistent with the minimal hepatic
TCDD levels. Hepatic vacuolization, characteristic of short-term exposure, subsided by 4 weeks. Similarly,
TCDD-elicited hepatic
necrosis and
inflammation dissipated by 1 week. Collectively, these results suggest that
TCDD-elicited histologic and gene expression responses can be correlated to elevated hepatic
TCDD levels, which, once eliminated, elicit minimal hepatic gene expression and histologic alterations.