Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures.

Chronic treatment of rats with acrylamide induces various tumors among which thyroid tumors are the most frequent. The aim of the present study was to develop an in vitro model of acrylamide action on thyroid cells to allow the investigation of the mechanism of this tumorigenic action. The first part of the study considered as targets, characteristics of thyroid metabolism, which could explain the thyroid specificity of acrylamide action: the cAMP mitogenic effect and the important H2O2 generation by thyroid cells. However, acrylamide did not modulate H2O2 or cAMP generation in the thyroid cell models studied. No effect on thyroid cell proliferation was observed in the rat thyroid cell line FRTL5. On the other hand, as shown by the comet assay, acrylamide induced DNA damage, as the positive control H2O2 in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in thyroid cell primary cultures. The absence of effect of acrylamide on H2AX histone phosphorylation suggests that this effect does not reflect the induction of DNA double strand breaks. DNA damage leads to the generation of mutations. It is proposed that such mutations could play a role in the carcinogenic effect of acrylamide. The mechanism of this effect can now be studied in this in vitro model.

Species specific thyroid signal transduction: conserved physiology, divergent mechanisms.

In the literature, data obtained in signal transduction from various species thyroids and cells lines are often integrated in a common model. We investigate qualitatively and systematically, using the same protocol, the control by TSH of the two main functions of the thyrocytes, the synthesis and the secretion of thyroid hormones. In all species investigated, the TSH receptor activates both. In some species, including humans, rats and mice, the TSH receptor activates both the cAMP and phospholipase C-PIP2 cascades, in others (e.g. dog) it only stimulates the first. The cAMP pathway activates the limiting step in thyroid hormones synthesis, the generation of H(2)O(2), in dog, rat and mice but not in human, pig, horse and beef. Thus although the physiological result of TSH action is the same in all species, the signaling pathways used are different. Other distinctions in signaling are observed such as the relative effects of one cascade on the other.