DNA Damage in Brain and Thyroid Gland Cells due to High Fluoride and Low Iodine

DNA Damage in Brain and Thyroid Gland Cells due to High Fluoride and Low Iodine

Jundong Wang College of Animal Science and Veterinary Medicine, Shanxi Agricultural University Taigu, Shanxi 030801, China
Yaming Ge College of Animal Science and Veterinary Medicine, Henan institute of science and technology, Henan 453003, China
Hongmei Ning  College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095,
China
Ruiyan Niu College of Animal Science and Veterinary Medicine, Shanxi Agricultural University Taigu, Shanxi 030801, China


COMMENTARY AND SUMMARY: Are We Creating Fluoride Madness?

This careful, responsible and utterly brilliant article focuses on the relationship between fluoride and iodine intake.   No, the experimental subjects are not humans; they are rats.  (You can’t do experiments like this on humans – not these days…thank God!)  Three key takeaway points:

Point #1 Cell Replication: Iodine, in the right amounts, allows for accurate, reliable cell duplication.  Hard to believe, but your body replaces about 50 billion cells a day.  If the duplication process is not 100% accurate, you get non-functional cells or cancer.  Iodine is critical to proper cell duplication.

Point #2 Evil Fluoride/Good Iodine: The article and its experiments show that the combination of excessive fluoride, and low iodine intake, is a double whammy for cell duplication.  Over 65% of the cells – in the experimental animals which had extra fluoride, and little iodine – were non-functional.  This is a track that leads to substantially lower intelligence, autism, ADHD, bad behavior, and non-functional children (and adults). And, ultimately, cancer, heart disease, obesity and COPD.

Point #3- Fluoride + Low Iodine = Illness & Stupidity: Perhaps (!) even low doses of fluoride in the presence of insufficient iodine, can cause terrible, permanent and irreversible damage to an infant brain, and also to any of the organs in an adult.  The result? Illnesses, cancer, heart disease, poor metabolism, obesity. Give your children quality bottled water, drink bottled water while you’re pregnant or pre-pregnant, and for God’s sake DONT mix infant formula with municipal tap water.

Impact on I.Q.?  Up to 25 I.Q. points.  That’s the difference between going to Harvard and failing to graduate from elementary school.  No kidding.  It’s that dramatic.  What do you want for your child?

Yes, there’s no question that fluoride does improve the health of teeth.  BUT AT WHAT PRICE?  With   some LOW intake level, yet unknown! – fluoride disrupts the safe and proper replication for many of those 50 billion cells daily that take over for their dying brother-cells.  Why play Russian Roulette with your children’s brains – or your own?

Fluoride might be good for your teeth, but poison for your brain, your blood, & your organs.

Like everything in life, science and disease management, the Law of Unintended Consequences is hiding behind the curtain.  If we didn’t eat “fast” (high glycemic) carbohydrates and sugars, our teeth would stop rotting, and we wouldn’t want, need, or tolerate fluoride – in toothpaste, water and air.

IN SUMMARY: it’s time to improve our diets, eat right (whole foods), and stop the fluoride madness. Start by taking enough iodine to counteract the problems caused by potentially excess fluoride.

Thyroid Iodine

Iodine is an essential element in thyroid hormones, which have a great  impact  on  the  development  and  functions of the central nervous system. Many studies have shown that in places prone to iodine deficiency, besides the prevalent problem of thyroid nodules, the intelligence quotient (IQ) of children was significantly lower than that in areas with sufficient iodine. Interestingly, high fluoride was also found to be a  contributing  factor.  Some  epidemiological studies have identified the combined interactive role    of high fluoride and low iodine for low IQ in children. Previous studies conducted in rats have mainly focused    on the interaction of high fluoride and low iodine and resulting oxidative stress for low IQ. Yet, we believe that the mechanism of their interaction is far more complex. Fluorine and iodine fall into the same category of halogen; therefore, fluorine can be easily absorbed and accumulated by the thyroid gland similar to iodine,  thus  interfering with iodine metabolism in the thyroid gland and resulting in iodine deficiency. Moreover, due to its active chemi- cal nature, fluoride can pass through both the blood–brain barrier and the placental barrier, and may induce DNA damage directly in cells. Thus, prolonged exposure to high fluoride and low iodine can lead to DNA damage in cells, especially brain and thyroid gland cells, in both parental generations and their offspring.

Abbreviations

F-                     Fluoride ion

HiF-LI         High fluoride plus low iodine

HiF              High fluoride

IQ               Intelligence quotient

LI                Low iodine

SCGE          Single cell gel electrophoresis

T3               Triiodothyronine

T4               Thyroxine

TSH            Thyroid-stimulating hormone

Introduction

Iodine is essential for the synthesis of the thyroid hormones – triiodothyronine (T3) and thyroxine (T4). An iodine-deficient diet results directly in decreased production of thyroid hormones, which adversely affects not only brain development, but also its functions such as attention, learning and memory. In areas with iodine deficiency, besides the occurrence of more frequent thyroid nodules, the intelligence quotient (IQ) of children is much lower than that in areas with adequate iodine.

However, recent studies reported an  inverse  relationship between early fluoride ingestion and intelligence, indicating a decrease of 8–10 IQ points in children living in villages with elevated fluoride intake. Epidemiological investigations also revealed that the differences in IQ in areas of both high fluoride and low iodine could be up to 25 points. Therefore, the interaction of high fluoride and low iodine becomes a major concern for researchers.

Clinical manifestations of fluorosis often occur in the hard tissues of animals, such as bones and teeth, as a result of long-term intake of elevated levels of fluoride, mainly due to industrial fluoride pollution. Evidence also indicates harmful effects of fluoride on soft tissues such as lung, kidney, testis, liver and brain. Generally, fluorine, in the form of the fluoride ion (F-), is present in soil and water  in low concentrations, but it may cause a threat to public and occupational health when its presence in the environment increases due to natural or anthropogenic sources. Excessive intake of F- via drinking water is an endemic problem in a number of countries including China,    India, and Mexico; several reports show that fluorosis and iodine deficiency coexist in some of these areas. Earlier studies have shown the effects of the interaction of high fluoride and low iodine on oxidative stress and antioxidant defense in the rat brain. This interaction causes a rapid increase in lipid peroxidation and a decrease in the antioxidant status of a cell, resulting in many types of lesions that cause DNA damage in cells in many organs.

The thyroid gland appears to be the most sensitive tissue in the body to F’. High F’ increases the concentration of thyroid-stimulating hormone (TSH) and decreases the

concentration of T3 and T4 hormones, thereby producing hypothyroidism in some populations. Consequently, pro- longed consumption of high F’ water is likely to suppress the function of both thyroid gland and brain. Therefore, DNA damage due to high fluoride and low iodine has become a focus of research in recent times.

The Test Method for DNA Damage

Single cell gel electrophoresis (SCGE) or comet assay is a simple, rapid and sensitive technique for measuring DNA dam- age. The alkaline version of the method (Singh and McCoy, 1988) is a very sensitive assay procedure for the detection of single-stranded breaks in DNA. SCGE was performed, essentially according to the published procedure with some modifications. At least 100 cells per slide per subject were analyzed (original magnification x200) under a fluorescent microscope (BX51, Olympus) equipped with a green light excitation and at 590-nm barrier filter. Comets form as the broken ends of a negatively-charged DNA molecule become free to migrate in the electric field toward the anode. The ratio of tailing was assessed by counting the tailing DNA in 100 cells per sample. Twenty-five cells were chosen randomly and photographed, to measure the length of DNA migration and to grade the cells in each sample. The extent of DNA damage was assessed from the length of DNA migration derived by subtracting the diameter of the nucleus from the total length of the image. The grading was as follows: grade I: tailing length/diameter of the nucleus  1; grade II: tailing length/diameter of the nucleus  2; grade III: tailing length/diameter of the nucleus  2. Grades I and II indicate generic rupture of the DNA chain. Grade III indicates apoptosis, presenting a small comet head and a large, bright tail that looks like a broom.

dna_000Experimental Evidence for DNA Damage in Brain and Thyroid Gland Cells

DNA damage in adult rat brain

To establish an animal model exposed to high fluoride and  low  iodine,  an  experimental  iodine-deficient diet was prepared from wheat, corn and soybean grown in  an iodine-deficient region – Weijiawan village of Anze County in the Shanxi province of China. These animals were given drinking water containing 150 mg/l NaF. The net content of iodine and fluoride in the experimental feed, and in the control feed, are listed in Table 67.1.

Thirty-two 1-month-old Wistar albino rats were ran- domly divided into four groups (Control, HiF group, LI group, HF-LI group) of six females and two males each, and maintained on the experimental diets and drinking water regimens shown in Table 67.1 under standard tem- perature (22–25°C), ventilation and hygiene conditions. At the age of 20 months, the rats were sacrificed for test- ing of their brain cells by SCGE. The results of the ratios of tailing, tail length and the proportion of grade III (most severe) migrated brain cells in different groups are listed as follows (Tables 67.2, 67.3 and Figure 67.1).

The rate and degree of DNA damage to brain cells in aged rats exposed to high fluoride, low iodine and their combined interaction were markedly higher,   especially in the HiF-LI group compared to other  experimental groups. This suggests that a low iodine intake, coupled with exposure to high fluoride, exacerbates lesions in the central nervous system.

 

DNA damage in adult rat thyroid gland cells

dna_001The method described above was used for testing DNA damage in thyroid gland cells; all the results obtained are presented in Tables 67.4, 67.5 and Figure 67.2. The results showed that DNA damage of thyroid gland cells exposed to high F, low iodine and the inter- action of both factors markedly increased, especially   in the HiF-LI group, with grade III damage up to 69.23%. It is noteworthy that iodine deficiency induces DNA damage of thyroid gland cells. These results support the earlier findings of Fang et al. (1994), showing a high incidence of thyroid cancer (15.6%) in iodine-deficient rats and mice compared to a zero percent incidence in controls.
 
 

DNA damage in offspring rat brain cells

During pregnancy, the thyroid gland needs to increase the production of thyroid hormone, which depends directly on sufficient supplementation of dietary iodine. Meanwhile, it has been observed that iodine in maternal milk responds quickly to iodine intake. Therefore, iodine deficiency is a threat to the development of the thyroid gland in the fetus and infants, and indirectly to their brain growth. On the other hand, fluoride can not only interfere with iodine in the thyroid gland, but can also adversely affect the brain development of offspring rats. To clarify the effects of high fluoride and low iodine on DNA damage in the brain of offspring rats, the following experiment was designed. 
All parent animals were treated with high fluoride and low iodine, as described earlier in this chapter. After 3 months of treatment, the female experimental animals were allowed to become pregnant by natural mating. The day of birth of the rat pups was regarded as day 0. During and after nursing, they were raised under conditions similar to those for their parents. After 1 month, the offspring rats were separated according to sex. At days 0, 10, 20, 30, 60, and 90, three male and three female rat pups were randomly selected from each litter for study of the DNA dam- age. The results of the ratios of tailing, tail length and the proportion of grade III (most severe) migrated brain cells in different groups are presented in Tables 67.6–67.8.

Thyroid IodineIngestion of high fluoride, low iodine, or a combination of high fluoride and low iodine showed significant effects on DNA damage in offspring rats up to day 90. However, the length of comet tail in brain cells exposed to low iodine was significant at day 20 and day 90, while the influence of high fluoride, and high fluoride and low iodine together, was significant over the entire period. Moreover, the proportion of grade III damage to brain cells increased considerably in all experimental groups, and an even greater effect was apparent with high fluoride and low iodine from day 0 to day 90, except on day 20. These results indicate that DNA strands in the brain cells of offspring rats in early life are adversely affected by exposure to high fluoride, low iodine and the combination of high fluoride and low iodine.

dna_003What Can We Learn From These Studies?

DNA damage of brain and thyroid gland cells exposed to high fluoride, low iodine and their combined interaction increased markedly, especially in the HiF-LI group. The possible mechanism of DNA damage induced by fluoride could be as follows. (1) Fluoride has a dense negative charge and is biochemically very active. Thus, it can have a direct effect on DNA, because of its strong affinity for uracil and amide bonds by —NH···F— interactions that can induce the rupture of hydrogen bonds in the base pairing of adenine and thiamine, resulting in disturbance of the synthesis of DNA and RNA and increasing error frequency of linkages between basic groups in the process of DNA replication. (2) Some studies also show that fluoride can combine stably with DNA by covalent bonding, affecting the normal structure of DNA. Alternatively, fluoride can induce the production of free radicals, which damage the DNA strands directly, or by lipid peroxidation initiated by the free radicals. (3) Fluoride may depress polymerase enzyme activity, which might further affect the process of DNA replication or repair.

Fluorine, being a halogen, is chemically related to iodine. However, it is much more chemically active than iodine, and therefore can interfere with iodine metabolism in the thyroid gland. Moreover, both iodine and fluorine have antagonistic effects on the thyroid gland. Goldemberg (1930) was the first to introduce fluorine therapy for hyperthyroidism and Basedow’s disease, on the assumption that simple goiter and cretinism were caused, not by iodine deficiency, but by a superabundance of F in air, food and water. Nevertheless, if the iodine content in water is already very low, compara- tively low concentrations of F in the drinking water may conceivably aggravate the effects of iodine deficiency on the thyroid. Thus, we suggest that F might directly damage cells and induce rupture of DNA strands, thereby causing dysfunction of the thyroid gland. Perhaps DNA damage is one of the reasons for the high morbidity rates among those afflicted with hypothyroidism goiter and subcretinism in high-fluorine and low-iodine areas.

Some reports also show that F’ can induce structural changes and dysfunctions in the thyroid gland. The thy- roid gland has a strong capacity for absorbing and accumu- lating F’. Fluorine content in the thyroid gland is reported to be second only to that of the aorta in nonbone tissues.

F’ can directly injure the structure of the thyroid follicle and induce cytoplasm reduction and karyopyknosis of fol- licular epithelial cells, reduce the number of microvilli on the cristae of epithelial cells, and lead to swelling of vacu- oles in follicular epithelial cells of the thyroid gland. Also, F disturbs the synthesis and secretion of thyroid hormone by interfering with the activity of enzymes that catalyze the conversion of thyroxine (T4) into the active thyroid hormone triiodothyronine (T3) and inactive metabolites, thereby  leading  to  perturbations  of  circulating thyroid hormone levels. Furthermore, excess F- also stresses the functional status of the hypothalamus–pituitary–thyroid system, thus adversely affecting the synthesis of DNA and RNA in thyroid cells.

In conclusion, excessive intake and accumulation of F- in the body not only affect the adult brain and thyroid structure, but also influence their development, especially in the case of iodine deficiency.

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References

Bachinskii, P.P., Gutsakeko, O.A., Narysaniuk, N.D., Sidora, V.D. and Shliakhta, A.I. (1985). Probl. Endokrinol. (Mosk) 31, 25–29.
Bobek, S., Kahl, S. and Ewy, Z. (1976). Endocrinol. Exp. (Bratisl.) 10, 289–295.
Bouaziz, H., Ammar, E., Ghorbel, H., Ketata, S., Jamoussi, K., Ayadi, F., Guermazi, F. and Zeghal, N. (2005a). Fluoride 37, 133–142.
Bouaziz, H., Soussia, L., Guermazi, F. and Zeghal, N. (2005b).
Fluoride 38, 185–192.
Cinar, A. and Selcuk, M. (2005). Fluoride 38, 65–68.
Dong, J., Yin, H.B. and Liu, W.Y. (2005). Neurotoxicology 26, 417–426.
Fang,   W.T.,   Qao,   B.S.,   Wang,   J.B.,   Hu,   P.Y.,   Yang,  X.X.
and Jiang, R.J. (1994). Zhonghua Zhong Liu Za Zhi 16, 341–344, in Chinese.
Gao, X.B., Liu, C.S., Sun, J.X., Zhang, N., Xu, Z. and Li,(1998). Carcinog. Teratog. Mutagen. 10, 28–30, in Chinese.
Ge, Y.M.,  Ning,  H.M., Wang,  S.L.  and Wang,  J.D.  (2005a).
Fluoride 38, 209–214.
Ge, Y.M.,  Ning,  H.M., Wang,  S.L.  and Wang,  J.D. (2005b).
Fluoride 38, 318–323.
Ge, Y.M.,  Wang,  J.D.,  Ning,  H.M.  and Wang,  S.L. (2005c).
Fluoride 38, 127–132.
Goldemberg, L. (1930). Presse Med. 102, 1751–1774. Hayashi, N. and Tsutsui, T. (1993). Mutat. Res. 290, 293–302.
Li, X.S., Zhi, J.L. and Gao, R.O. (1995). Fluoride 28, 189–192.
Li, Y., Dunipace, A. and Stookey, G.K. (1987). Mutat. Res. 190, 229–236.
Lin,  F.F.,   Aihaiti,  Zhao,  H.X.,  Lin,  J.,  Jiang,  J.Y.,   Ma,     L.,
Maimaiti, T.E.X., Ai, K. and Di, B. (1991). Endem. Dis. Bull. 6, 62–68, in Chinese.
Liu, G.Y., Chai, C.H.Y. and Kang, S.H.L. (2002). Chin. J.  Vet.
Sci. 22, 512–514, in Chinese.
Lu, Y., Sun, Z.R., Wu, Z.N., Wang, X., Lu, W. and Liu, S.S. (2000). Fluoride 33, 74–78.
McLaren, J.R. (1976). Fluoride 9, 105–116.
Hassanien, M.H., Hussein, L.A., Robinson, E.N. and Preston Mercer, L. (2003). J. Nutr. Biochem. 14, 280–287.
Monsour, P.A. Kruge, B.J. (1985). Fluoride 18, 53–61.
Refsnes, M., Kersten, H., Schwarze, P.E.  and Lag, M.   (2002).
Ann. N.Y. Acad. Sci. 973, 218–220.
Refsnes, M., Schwarze, P.E., Holme, J.A. and Lag, M. (2003).
Hum. Exp. Toxicol. 22, 111–123.
Schuld, A. (2005). Fluoride 38, 91–94.
Shashi. Fluoride 21, 137–140.
Singh, N.P. and McCoy, M.T. (1988). Exp. Cell. Res. 175, 184–189.
Susheela, A.K., Bhatnagar, M., Vig, K. and Mondal, N.K. (2005). Fluoride 38, 98–108.
Trabelsi, M., Guermazi, F. and Zeghal, N. (2001). Fluoride 34, 165–173.
Wang, A.G., Xia, T., Chu, Q.L., Zhang, M., Liu, F., Chen, X.M. and Yang, K.D. (2004). Biomed. Environ. Sci. 17, 217–222.
Wang,  J.D.,  Ge, Y.M.,  Ning,  H.M.  and Wang,  S.L. (2004a).
Fluoride 37, 201–208.
Wang,  J.D.,  Ge, Y.M.,  Ning,  H.M.  and Wang,  S.L. (2004b).
Fluoride 37, 264–270.
Wang,  J.D.,  Guo,  Y.H.,  Liang,  Z.X.  and  Hao,  J.H. (2003).
Fluoride 36, 177–184.
Wang, J.D., Hong, J.H., Li, J.X. and Cai, J.P. (1994). Fluoride 27, 136–140.
Wang, J.D., Hong, J.H., Li, J.P., Guo, Y.H., Zhang, J.F. and Hao, J.H. (2002). Fluoride 35, 51–55.
Wang, J.D., Hong, J.P. and Li, J.X. (1995). Fluoride 28, 131–134. Wang, J.D., Zhang, C.W.,  Chen, Y.F.,  Li, J.X., Hong, J.P.    and
Wang, W.F. (1992). Fluoride 25, 123–130.
Wang, Y.Y.,  Zhao, B.L., Li, X.J., Su, Z. and Xi, W.J.    (1997).
Fluoride 30, 5–15.
Xu, H., Jin, X.Q., Jing, L. and Li, G.S. (2006). Biol. Trace Elem.
Res. 109, 55–60.
Yu, R., Xia, T.,  Wang, A. and Chen, X. (2002). Chin. J.    Prev.
Med. 36, 219–221, in Chinese.
Zhan, X.A., Wang, M., Xu, Z.R., Li, W.F.  and Li, J.X.  (2006).
Arch. Toxicol. 80, 74–80.
Zhang, J.H., Liang, C., Ma, J.J., Niu, R.Y. and Wang, J.D. (2006). Fluoride 39, 126–131.
Zhang, J.H., Wang, J.D., Pang, Q.H. and Lang, Z.X. (2004). Proceedings of the 2nd National Conference on the History    of Toxicology and Control of Paroxysmal Poisoning; June. Xi’an, Shaanxi, China, pp. 20–24 [in Chinese].
Zhao, L.B., Liang, G.H., Zhang, D.N. and Wu,  X.R.    (1996).
Fluoride 29, 190–192.

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