Abstract | INTRODUCTION: A study was conducted on histological patterns and biomolecular changes in Goitrogen-induced experimental rat thyroid tumors. The link between the histological types observed and N-ras, B-raf, and PI3KCA gene mutations widely reported in human thyroid cancers was explored. MATERIAL AND METHODS: An analysis was done on paraffin-embedded tumor tissue sections from Wistar rats receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking-water supply over an 18-month period. Three experimental subgroups were formed, each comprising 10 thyroids: subgroup I (control) consisted of thyroids from untreated controls; subgroups II and III (experimental) consisted of thyroids from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no metastasis (II), or distant metastasis (III). DNA was extracted from paraffin-embedded tissues. To test for the genetic mutations most widely reported in human thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and exon 15 of the B-raf gene were amplified and sequenced. RESULTS: All tumors were of the follicular type. None of the 20 experimental rat thyroids displayed the expected gene mutations reported in humans. However, 90% of them contained four new B-raf gene mutations and all were silent and did not cause an amino acid substitution in the protein chain. CONCLUSIONS: Biomolecular analysis suggested that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor formation using the experimental procedure applied in this study. But the four mutations in B-raf, though without functional repercussions, may be a specific marker for this tumor type.
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Authors | María Inés Carmona-López, Manuel De Miguel, Hugo Galera-Ruiz, María José Ríos-Moreno, Ana Fernández, Hugo Galera-Davidson |
Journal | Endocrine research
(Endocr Res)
Vol. 37
Issue 4
Pg. 188-96
( 2012)
ISSN: 1532-4206 [Electronic] England |
PMID | 22630346
(Publication Type: Journal Article)
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Chemical References |
- Perchlorates
- Potassium Compounds
- potassium perchlorate
- Braf protein, rat
- Proto-Oncogene Proteins B-raf
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Topics |
- Adenocarcinoma, Follicular
(chemically induced, genetics, pathology)
- Animals
- Base Sequence
- Exons
- Female
- Genes, ras
- Humans
- Molecular Sequence Data
- Mutation
- Perchlorates
(toxicity)
- Potassium Compounds
(toxicity)
- Proto-Oncogene Proteins B-raf
(genetics)
- Rats
- Rats, Wistar
- Sequence Analysis, DNA
- Signal Transduction
(drug effects, genetics)
- Thyroid Neoplasms
(chemically induced, genetics, pathology)
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