Presta M, Zavanella T, Mazzocchi C, Ziliani S, Mazzoleni G, Calovini D, Braga M, Ragnotti G
Toxicol Pathol. 1984;12(1):49-55. doi: 10.1177/019262338401200108.
The beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol (ZAMI 1305), oncogenic to the liver of the female but not of the male Wistar rat, was used to investigate some aspects of the relationship between liver and thyroid during chemical hepatocarcinogenesis. Thyroidectomy (TDX) strongly reduces the amount of hepatic DNA damage induced by a single administration of ZAMI 1305 in the female Wistar rat. One week of treatment with triiodothyronine (T3) completely restores the susceptibility of the liver of thyroidectomized animals to the genotoxic activity of the molecule. The amount of hepatic DNA damage in intact females varies with the age of the animal, being maximal in rats of 4-8 weeks of age, when T3 serum concentration are also maximal. An increase of relative thyroid weight, coupled with histological hyperplasia of the gland, is observed in female Wistar rats treated for 6 months with ZAMI 1305. Minimal changes of the thyroid are observed in ZAMI 1305-treated male rats. The increase of relative thyroid weight in female rats appears to be related to the severity of preneoplastic and neoplastic liver changes. These findings and several suggestions from the literature lead us to propose a model for the interaction between liver and thyroid during chemical hepatocarcinogenesis.
β-阻滞剂DL-1-(2-硝基-3-甲基苯氧基)-3-叔丁氨基丙-2-醇（ZAMI 1305）对雌性Wistar大鼠肝脏具有致癌性，而对雄性则无，本研究用其探究化学性肝癌发生过程中肝脏与甲状腺之间关系的某些方面。甲状腺切除术（TDX）可显著降低雌性Wistar大鼠单次给予ZAMI 1305后诱导的肝脏DNA损伤量。用三碘甲状腺原氨酸（T3）治疗一周可完全恢复甲状腺切除动物肝脏对该分子遗传毒性活性的敏感性。完整雌性大鼠肝脏的DNA损伤量随动物年龄而变化，在4至8周龄大鼠中最大，此时血清T3浓度也最高。用ZAMI 1305治疗6个月的雌性Wistar大鼠出现相对甲状腺重量增加，同时伴有甲状腺组织学增生。ZAMI 1305处理的雄性大鼠甲状腺变化最小。雌性大鼠相对甲状腺重量的增加似乎与癌前和肿瘤性肝脏变化的严重程度有关。这些发现以及文献中的一些建议促使我们提出化学性肝癌发生过程中肝脏与甲状腺相互作用的模型。
