Intake of Boron, Cadmium, and Molybdenum enhances rat thyroid cell transformation

Abstract

BackgroundEpidemiologic data in volcanic areas suggest that environmental factors might be involved in the increase of thyroid cancer (TC) incidence. Recent reports indicate that several heavy metals and metalloids are increased in volcanic areas. This study aims to evaluate the combined effect of three of these elements Boron (B), Cadmium (Cd), and Molybdenum (Mo) - all increased in the volcanic area of Mt. Etna, in Italy - on thyroid tumorigenesis in the rat.MethodsFemale Wistar rats prone to develop thyroid tumors by low-iodine diet and methimazole treatment received ad libitum drinking water supplemented with B, Cd, and Mo at concentrations in the range found in the urine samples of residents of the volcanic area. At 5 and 10 months animals were euthanized, and their thyroid analysed. Statistical analysis was performed with a 2-way unpaired t-test.ResultsNo toxic effect of the three elements on the growth of the animals was observed. A significant increase of histological features of transformation was observed in thyroid follicular cells of rats treated with B, Cd, and Mo compared with those of control group. These abnormalities were associated with decreased iodine content in the thyroid.ConclusionsThis study provides the evidence that slightly increased environmental concentrations of B, Cd, and Mo can accelerate the appearance of transformation marks in the thyroid gland of hypothyroid rats.

Content of 31 trace elements in thyroid malignant nodules and thyroid tissue adjacent to nodules investigated using neutron activation analysis and inductively coupled plasma mass spectrometry

“…Mo-dependent enzymes operate in the oxidative system of thyroid epithelial cells and also play role in the release of T3 from the thyroid gland. However, there is data that even a slight increase Mo in the diet may accelerate and/or promote the process of thyroid cell transformation, thus acting as a tumor-promoting agent rather than a carcinogen [94]. Why Mo content in TMNs is higher than normal level and how an excess of Mo acts on thyroid are still to be cleared.…”

Heavy Metals in the Environment and Thyroid Cancer

“…In the latter, three metals, B, Mo, and Cd, were added to the drinking water at a concentration double that measured in the urine of the residents of the Mt. Etna volcanic area [84]. These metals were chosen not only because they were markedly elevated in the water of the volcanic area relative to the water of the control area in Sicily (Mo and Cd), but also because they were among the few metals exceeding the urine reference limit in more than 20% of residents of the volcanic area (B) [25].…”

“…After 10 months, however, there were marked differences in the histological morphology of the thyroid: In addition to an evident disorganization of the follicle structure and the presence of hyperplastic and oxyphilic cells (both signs typical of chronic hypothyroidism caused by goitrogens), there were more papillary structures in the thyroid (present in all metal-treated animals vs. only one case in the control group). In addition, abnormal nuclear morphology and nuclear pseudo-inclusions were present in the thyroid of metal-treated animals [84]. B and Mo concentrations in the thyroid were not different between the two groups, while Cd was undetectable and the iodine content was reduced in the thyroid of treated animals, suggesting a possible chronic influence of the metal mixture on the thyroid iodine uptake or retention [84].…”

“…In addition, abnormal nuclear morphology and nuclear pseudo-inclusions were present in the thyroid of metal-treated animals [84]. B and Mo concentrations in the thyroid were not different between the two groups, while Cd was undetectable and the iodine content was reduced in the thyroid of treated animals, suggesting a possible chronic influence of the metal mixture on the thyroid iodine uptake or retention [84].…”

Increased Thyroid Cancer Incidence in Volcanic Areas: A Role of Increased Heavy Metals in the Environment?

“…Female rats were supplied with a goitrogenic diet, and B, Cd, and Mo were added to their drinking water at concentrations twice as high those measured in the urine of the residents of the volcanic area in Sicily. The thyroids of treated animals examined after 5 and 10 months of exposure exhibited progressive increases in follicular dyshomogeneity, nuclear pseudoinclusions, and papillary structures compared to the thyroids of the control rats (also hypothyroid under the goitrogenic diet) [119]. Papillary structures associated with nuclear aberrations are considered preneoplastic features of the thyroid.…”