Reversibility of Proliferative Thyroid Lesions Induced by Iodine Deficiency in a Laboratory Zebrafish Colony

Abstract

A laboratory zebrafish colony developed red masses, predominantly under the jaw, in a significant portion of the population. The masses were diagnosed histopathologically as thyroid follicular hyperplasia, adenoma, or carcinoma in accordance with published morphologic criteria. After switching to a higher iodine brand of salt used to maintain a low level of salinity within the water system and a small diet change, the thyroid lesions regressed dramatically. Within 5 months the masses were no longer grossly visible. At the population level, external evaluations and histopathological assessments of whole-body sections document a regression in the prevalence of thyroid neoplasia and hyperplasia to normal thyroid conformation by 11 months after salt change. These findings suggest that a wide range of proliferative thyroid lesions, including neoplasms, in zebrafish may be hormone-dependent, even following lesion development. In addition, these results suggest that zebrafish have an adaptive ability to absorb iodine from water and food, which should be considered in discussions to standardize diets and when describing environmental parameters in publications.

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology

“…These thyroid tumors are TSH-dependent but often metastasize to lymph nodes [155] and the lungs [155,174,185], although the tumor cells can be converted to TSH-independence via continuous subpassage in culture [155,174,177,178,183]. The hormone dependency of thyroid tumors, including adenocarcinomas, also occurs in a Zebrafish colony as feeding the fish with salt that contains iodine causes regression of the tumors [197]. In 1953, Furth wrote that "conditions can be created whereby uncontrolled proliferation of one cell type is obtained, resulting in a tumor-like growth.…”

“…Another major piece of evidence invigorating the non-mutation theory comes from the studies showing the reversibility of transformed cells back to the normal in cell culture [446,453,620,[688][689][690][691] and in animals or humans [197,370,[692][693][694][695], with or without induction by chemicals [696][697][698][699][700][701][702][703][704]. Actually, this reversion has received attention for almost a century [446,688,689], in part because direction of cancer cells to differentiation is a tantalizing strategy for cancer therapy.…”

Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007–2012

“…Nevertheless, these connections were not observed in iodine-deficient adults. The major reason for explaining this result is that iodine deficiency results in reduced circulating TT3 and TT4 and increased TSH, which weakens the effect of dietary selenium intake on thyroid hormones ( 42 ).…”

Mutation or not, what directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown and should be prioritized in our research

“…Ever since almost a century ago [514][515][516], there have already been a battery of studies showing that certain extrinsic factors, such as some drugs or nucleic acids [385,[517][518][519][520][521][522][523][524][525][526][527][528][529], can facilitate the reversion of cancer cells back to normal via differentiation or maturation [89,[514][515][516][530][531][532] in culture dishes, in animals, or in patients [468,496,[533][534][535][536]. Neural differentiation of the PC12 rat pheochromocytoma cell line induced by nerve growth factors or some chemicals is among the best-studied examples [537][538][539].…”