Fan F, Rozman K K
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City.
Toxicol Lett. 1995 Jan;75(1-3):209-16. doi: 10.1016/0378-4274(94)03182-7.
The aim of this study was to examine short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Long-Evans (L-E) rats. In the short-term study, female rats were dosed orally with 5.3, 12, 18 and 60 micrograms TCDD/kg and sacrificed 4 days after dosing. In the long-term study, rats were dosed with 27, 40 and 60 micrograms TCDD/kg and sacrificed 90 days after dosing. Four days after dosing, ethoxyresorufin O-deethylase (EROD) activity was fully induced at all doses studied, hepatic phosphoenolpyruvate carboxykinase (PEPCK) and gamma-glutamyl transpeptidase (gamma-GT) activities were dose-dependently reduced, whereas hepatic tryptophan 2,3-dioxygenase (TdO) activity was stimulated at low doses but decreased at high doses. Serum total T4 (TT4) levels were dose-dependently decreased, whereas serum total T3 (TT3) and tryptophan levels were unaffected. The short-term effects of TCDD examined in this study indicate only small differences in the response of female L-E rats to TCDD as compared to males. Ninety days after dosing, liver EROD activity revealed considerable reversibility although it was still elevated compared to controls. Hepatic PEPCK activity at this time point was no more different from controls. In contrast to 4 days after dosing, serum TT3, TT4 and hepatic gamma-GT activity were dose-dependently elevated at the 90-day time point. These findings have significant implications for the interpretations of subchronic and chronic effects of TCDD on thyroid homeostasis and on the formation of preneoplastic liver foci.
本研究的目的是检测2,3,7,8-四氯二苯并-对-二噁英（TCDD）对雌性Long-Evans（L-E）大鼠的短期和长期生化影响。在短期研究中，给雌性大鼠口服5.3、12、18和60微克TCDD/千克，给药4天后处死。在长期研究中，给大鼠口服27、40和60微克TCDD/千克，给药90天后处死。给药4天后，在所研究的所有剂量下，乙氧基异吩唑酮O-脱乙基酶（EROD）活性均被完全诱导，肝磷酸烯醇式丙酮酸羧激酶（PEPCK）和γ-谷氨酰转肽酶（γ-GT）活性呈剂量依赖性降低，而肝色氨酸2,3-双加氧酶（TdO）活性在低剂量时受到刺激，但在高剂量时降低。血清总T4（TT4）水平呈剂量依赖性降低，而血清总T3（TT3）和色氨酸水平未受影响。本研究中检测的TCDD的短期影响表明，与雄性相比，雌性L-E大鼠对TCDD的反应仅存在微小差异。给药90天后，肝脏EROD活性显示出相当大的可逆性，尽管与对照组相比仍有所升高。此时肝PEPCK活性与对照组无差异。与给药4天后相反，在90天时血清TT3、TT4和肝γ-GT活性呈剂量依赖性升高。这些发现对解释TCDD对甲状腺稳态和癌前肝病灶形成的亚慢性和慢性影响具有重要意义。
