Liver DNA Damage by Chemical Carcinogens: Role of Thyroid Hormones
In 1948, Paschkis et al.14 demonstrated the protective effect of thiouracil on the induction of liver tumors by 2-acetylaminofluorene. Since then, several authors reported on the inhibition of hepatocarcinogenesis in hypothyroid rats1,2,8,12,19. These findings raise the point of the identification of the stage in chemical hepatocarcinogenesis which is inhibited by thyroid deficiency. Even though it has been demonstrated that thyroid digest increases the rate of growth of liver tumors in pituitary dwarf mice treated with aminofluorene3, therefore suggesting a role for thyroid hormones in the promotion and/or progression of liver tumors, several data indicate that thyroid activity might influence liver carcinogenesis also at the stage of initiation. Bielschowsky and Hall1, in fact, demonstrated that thyroidectomy, performed before, but not after, the administration of the carcinogen, prevents the development of liver tumors. These findings were confirmed by Goodall8 who demonstrated that in thyroidectomized animals the treatment with thyroid digest performed after aminofluorene administration does not restore the suscciptibility to the carcinogen. Moreover, thyroid hormones have been demonstrated to be necessary for the in vitro transformation of cultured cells by x-rays or chemical carcinogens9,10.
KeywordsThyroid Hormone Liver Tumor Genotoxic Activity Epoxide Hydrolase Activity Microsomal Mixed Function Oxidase
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