Fluoride doped hydroxyapatite in soft tissues and cancer

Fluoride doped hydroxyapatite in soft tissues and cancer.

Fluoride doped hydroxyapatite in soft tissues and cancer. A literature review.

Abstract

Inorganic Fluorides are potent bio-accumulative poisons with no nutritional value and there is
abundant evidence from the published literature that they are genotoxic carcinogens affecting
numerous organs. Fluoride interferes with the tumour suppression by Melatonin. Fluoride will
increase the deposition of Hydroxyapatite crystals in the tissues and these crystals accelerate
malignant cancer growth.
Keywords: Bone, Brain, Breast, Cancer, Cervix, Clastogen, Colon, DNA Damage, Endocrine Disruptor,
Fluoride, Fluoridation, Genotoxin, Hydroxyapatite, IGF, Kidney, Liver, Lung, Melanoma, Melatonin,
Micronuclei, Oral, Pituitary adenoma, Pharynx, Prostate, Rectum, Stomach, Thyroid, Uterus

Introduction

Fluorides are so highly toxic that a single truckload of the industrial waste from the phosphate
fertilizer industry, used to fluoridate public drinking water, is sufficient to kill the whole Australian
populace outright. The largest recorded knock down of humans, animals and crops by Fluoride was
the eruption of Lakagígar in Iceland over an eight-month period between 1783 and 1784, where a
mixture of Hydrogen Fluoride and Sulfur Dioxide is estimated to have claimed up to 6 million lives
directly or indirectly (through starvation due to loss of livestock and crops) in the Northern
Hemisphere [Wikipedia 2015].
Humans and farm animals have not evolved to deal with Fluoride intoxication as have some other
organisms [Li 2013] and recent studies have shown how the cells of these organisms can eject the
toxin through specific ion channels [Stockbridge 2015]. It is a general rule that such highly toxic
elements are carcinogenic and this review looks at the evidence that has been published with an
emphasis on more recent findings.
The literature found on Fluoride includes descriptive terms including:
– Cytotoxin
 Clastogen
– Mitogen
– Genotoxin
– Carcinogen
– Mutagen
– Low-dose Endocrine Disruptor

Weight of Evidence for Fluoride as a Carcinogen

In order to assess the plausibility of inorganic Fluoride compounds as carcinogens, it is necessary to study Fluoride toxicology details at all levels:
Molecular how does Fluoride act on your hormones, enzymes, DNA, RNA?
Organelle e.g. how are mitochondria affected by Fluoride?
Cellular How do cells transport, metabolize and eject Fluoride, in vivo and in vitro?
Organ How are organs damaged by Fluoride?
Animal studies Essential to measure chronic disease, death.
Case studies Individual exposure, acute and chronic, genetic sensitivity, vulnerability
Clinical trials adverse outcomes, side effects
Bioaccumulation Autopsies and detailed examination of tumours
Epidemiology Correlations and associations, hints of causes, time progression and industrial exposure.
The literature on Fluoride toxicology is a huge resource, growing at about 500 peer-reviewed papers
per year. Therefore this brief review is intended as a pointer for those interested to read in detail the
output of the hundreds of scientists who have addressed the cancer associations using one or more
of the above approaches.
Excellent reviews of Fluoride Toxicology and Fluoridation with reference to cancer are available
[Bryson 2004, Burk 1977, Cohn 1992, Connett 2010, Doull 2006, Hirzy 2013, Ozsvath 2009, Prystupa
2001, Thiessen 2011, 2014, Waugh 2014, Yiamouyiannis 1977, 1993].
The greatest and most easily accessed source is the online encyclopaedia established by the Fluoride
Action Network and readers are encouraged to use the search function there for in-depth discussion
of material summarized here [www.fluoridealert.org].
An important variable in all cancer studies, often not determined, is total dietary intake of Fluoride,
with tea and toothpaste as major contributors.
A significant exposure route, often overlooked, is the direct absorption of Fluoride through the oral
cavity tissues, i.e. it is not necessary to swallow toothpaste or mouth rinse to be poisoned.
A mortality and malignant neoplasm analysis found no significant increase due to fluoridation
[Erickson 1978].
More recently an analysis of cancer incidence rates and water fluoridation status of 21.8 million
Americans found Fluoridated drinking water was positively associated with cancer of oral cavity and
pharynx, colon, rectum, hepato-biliary and urinary organs [Takahashi 2001]. Further details of this
important study will be mentioned in the following description of literature found for each organ.
 

DNA Damage by Fluoride

Recent studies have revealed great genetic differences in the ability of organisms to excrete fluoride,
making comparison of genotoxic tests at different concentrations of this toxin difficult [Crespi 1990,
Rivedal 2000, Li 2013, Stockbridge 2015]. Ape and human cells show greater susceptibility to
Fluoride’s mutagenic effects than rodent cells [Kishi 1993, Manivanan 2012].
Extensive in vivo and in vitro studies of DNA damage by Fluoride are available [Tazhibaev 1977, Pati
1987, Jones 1988, Lasne 1988, Suzuki 1989, NAS 1993, Oguro 1995, Wu 1995, Gadhia 1997, Erciyas
2009, Flora 2012].
Some evidence that Stannous Fluoride is mutagenic was found as early as 1976 [Gocke 1981].
Fluoride increases the frequency of mutations at the thymidine kinase locus in cultured mouse
lymphoma and human lymphoblastoid cells [Caspary 1987, Cole 1986, Crespi 1990]. A significant
increase in micronucleated polychromatic erythrocytes was observed [Suzuki 1991].
Fluoride was found to be clastogenic to cultured human diploid cell (IMR-90) [Hayashi 1993, Oguro
1995]. Increased sister-chromatid exchange is observed in high fluoride exposed human
communities [Sheth 1994, Wu 1995, Meng 1995, Meng 1997, Lazutka 1999, Joseph 2000].
Significant increases in the frequencies of chromosome aberrations were induced by Fluoride in
cultured rat vertebral cells [Mihashi 1996]. Even at low doses, chromosome aberrations were
observed in cultured rat bone marrow cells treated with fluorides [Khalil 1995]. DNA damage,
apoptosis and cell cycle changes are induced by fluoride in rat oral mucosal cells and hepatocytes
[He 2006].
Mechanisms for DNA damage by Fluoride have been discussed [Aardema 1989, Aardema 1995].
Studies using human cell lines in vitro are available [Lestari 2005, Zhang 2009].

Fluoride and Insulin-like Growth Factor

Fluoride treatment increases serum insulin-like growth factor IGF-1 [McClintock 1997].
Recombinant human insulin-like growth factor (IGF) binding protein-3 has been found to stimulate
prostate carcinoma cell proliferation via an IGF-dependent mechanism [Angelloz-Licoud 1996].

Fluoride and Melatonin Suppression

Melatonin, produced in the Pineal Gland and many other organs, maintains the circadian rhythm, is
protective against oxidative stress by scavenging free radicals, binds Calmodulin and blocks
activation of oestrogen receptor-alpha [Kearney 2015]. It has been shown to suppress tumor growth
in cancers of the bone [Koyama 2002], the breast [Blask 1988, Lenoir 2005] and liver [Rahman 2003].
Melatonin inhibition of cancer growth in vivo involves suppression of tumor fatty acid metabolism
via melatonin receptor mediated signal transduction [Blask 1999].
Melatonin has been found to be an endogenous-specific inhibitor of estrogen receptor via
Calmodulin [del Río 2004].
Melatonin has been found to reduce fluoride-induced genotoxicity in human peripheral blood
lymphocyte cells [Rao 2006, Rao 2013, Thakur 2014].
Fluoride is bio-accumulative in the Pineal Gland via calcification with formation of Fluoride doped
Hydroxyapatite Ca3(PO4)2·Ca(OH,F)2[Luke 1998]. Evidence suggests that this calcification by Fluoride
reduces Melatonin production with age, thereby increasing malignant cancer growth [NRC 2006].

Bladder Cancer

The bladder is one of the organs exposed to high Fluoride concentrations as the human body ejects
most of the toxin via the kidneys in urine.
Significantly higher rate of bladder cancer was found in fluoridated communities [Takahashi 2001,
Yang 2000].
Industrial exposure to airborne Fluoride is associated with elevated bladder cancer rates
[Romunstad 1999, 2000, Grandjean 2004]. The Republic of Ireland (fluoridated) has a higher
incidence of bladder cancer than Northern Ireland (not fluoridated) [Waugh 2014].

Bone Cancer

The association between Fluoride and the relatively rare bone cancers (including Ewing sarcoma and
osteosarcoma) has received considerable study, perhaps because of the obvious unwanted
damaging cell proliferation that results in dental fluorosis [Wergedal 1988, Mahoney 1991, Cohn
1992, Lee 1993, Comber 1995, Khalil 1995, Rao 1995, Hsu 1999, Takahashi 1999, Ramesh 2001,
Koyama 2002, Zhang 2006, Eyre 2009, Ottaviani 2009, Mirabello 2009 and 2011, Podder 2011,
Sandhu 2011, Pathi 2011, Kharb 2012, Levy 2012, Huo 2013, Blakey 2014, Loder 2015].
Fluoride causes osteoblast proliferation and malignant transformation [Wergedal 1988, Zhang 2006].
A very useful set of articles on Fluoride and bone cancer is available [Lee 1993 and others]. Problems
identified with this rare cancer include reclassification of body sites to cell types in the 1970s,
making it impossible to compare some sets of incidence statistics.
A dose-dependent increase of osteosarcoma was seen in the bones of fluoride-treated male rats
[NTP 1990] and mice [Maurer 1990]. Significantly higher rate of bone cancer was found for males in
fluoridated communities [Yiamouyiannis 1993, Takahashi 2001]. Increased osteosarcoma in young
males was reported in fluoridated areas [Bassin 2001, 2006]. The sex-dependent variability was also
examined and 15-19 year-old males were at higher risk to osteosarcoma than females in the same
age group (p<0.001) but no association with water fluoridation status was found [Levy 2012]. Dietary

Fluoride intake was not examined.

A study of osteosarcoma and Ewing sarcoma found that both are more prevalent in males, but did
not find evidence of increased rates in fluoridated areas [Blakey 2014]. The authors point out the
difficulties of dealing with such rare cancers and the lack of information on total dietary intake of
Fluoride and the widespread use of fluoridated toothpaste over the study period of 1980 to 2005.
A significant association between Fluoride in drinking water and osteosarcoma was found [Kharb
2012, Sandhu 2011]. Examination of osteosarcomas found no significant elevation of Fluoride within
the tumours [Kim 2011], suggesting that Fluoride simply initiates the cancer. A study based on only
130 subjects claimed to have found a protective effect of Fluoride against osteosarcoma [Gelberg
1995]. Difficulty with small numbers of cases was also found in Ireland [Comber 2011].
Induction of apoptosis by sodium fluorosilicate has been demonstrated in human osteogenic
sarcoma [Song 2005].
Many of the studies of bone cancers do not mention exposure to bone-seeking radionuclides which
are known contaminants in the industrial fluoride waste used to fluoridate water.

Brain and Pituitary Gland Cancer

Significantly higher rate of brain cancer was found in fluoridated US communities [Takahashi 2001].
The Republic of Ireland (fluoridated) has a higher incidence of central nervous system cancer than
Northern Ireland (not fluoridated) [Waugh 2014].
Fluoride impact via DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in
primary cultured rat hippocampal neurons has been studied [Zhang 2008]. Sodium Fluoride
induction of stress response and differential expression of 70 kDa stress proteins in HeLa and rat
brain tumor 9L cells has been reported [Cheng 1998].
Various agents have been investigated to ameliorate brain damage by Fluoride [Pal 2014].
Anecdotal evidence of increased brain cancer from industrial Fluoride exposure requires further
investigation [Gasser 2011].
A cluster of pituitary adenomas in workers in the aluminum industry exposed to Fluoride has been
reported [Cullen 1996].

Breast Cancer

Breast cancer is the second leading cause of cancer death among women, causing almost 40,000
deaths in USA in 2011.
It is an open question to determine how human mothers largely succeed in preventing delivery of
toxic Fluoride to their babies through breast milk, given that the placenta provides no barrier. One
probable explanation is bio-accumulation of Fluoride in breast tissue in the form of Fluoride doped
Hydroxyapatite. The deposition of Hydroxyapatite in abnormal locations has been recognized as a
major health issue for some time [Garcia 2003].
One significant feature of breast cancer diagnosis is the presence of calcium deposits (averaging 0.3
mm3 in size) detected via mammograms [Castronovo 1998, Cooke 2003].
Both Calcium Oxalate and Calcium Hydroxyapatite have been detected in breast tissue, however
only the Hydroxyapatite is associated with malignancy [Wilson 2014].
Calcium Hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human
breast cancer cell lines [Morgan 2001, 2005].
A significant study followed up 61,433 women who were cancer free at baseline in 1987-1990.
Over a mean follow-up of 17.4 years, there were 2,952 incident cases of invasive breast cancer
identified. Coffee consumption was not associated with risk of overall breast cancer (multivariate
relative risk (RR) for ≥ 4 cups/day versus <1 cup/day = 1.02; 95% CI, 0.87-1.20) or with any subtype
defined by ER and PR status. Black tea (containing large amounts of Fluoride) consumption was
significantly positively associated with risk of overall breast cancer (RR 1.22 95% CI 1.05-1.40) and
ER+/PR+ tumors (RR 1.36 95%CI 1.09-1.69) [Larsson 2009].
A recent meta-analysis of prospective studies involving over 3 million subjects and 49,000 cancer
cases also found an increased risk of breast cancer associated with drinking 3 cups or more of black
tea (RR 1.18 95%CI 1.05 -1.32) [Yu 2014].
Humoral bone morphogenetic protein 2 (BMP2) has been shown to induce breast cancer
microcalcification [Liu 2008]. BMP expression has been shown to be increased by Fluoride [Huo
2013].
Hydroxyapatite enhances the mitogenesis of mammary cells, amplifying the malignant process and
resulting in accelerated tumor growth [Wilson 2014]. Synthetic Hydroxyapatite nanoparticle-
containing scaffolds have been used to study induction of breast cancer bone metastasis [Pathi
2011].
Due to rapid surface substitution of hydroxyl groups of Hydroxyapatite by Fluoride under mild
conditions, breast cancer diagnosis has been demonstrated via PET imaging of microcalcifications
caused Fluoride by using radioactive 18F-NaF [Wilson 2014].
Extracellular calcium has been shown to promote the migration of breast cancer cells through the
activation of the calcium sensing receptor [Saidak 2009].
Melatonin suppression of breast cancer has been studied [Lenoir 2005] and as mentioned above,
Fluoride suppression of Melatonin will increase breast cancer incidence.

Cervical and Endometrial Cancer

Factors involved in cervical and endometrial cancer include calcium uptake, Vitamin D and hypoxia
[McCullough 2008, Moreno-Merlo 1999]. The Republic of Ireland (fluoridated) has a higher incidence
of cervical cancer than Northern Ireland (not fluoridated) [Waugh 2014].

Colon and Rectum Cancer

Significantly higher rate of colon and rectum cancer was found in fluoridated communities
[Takahashi 2001]. The Republic of Ireland (fluoridated) has a higher incidence of colon cancer than
Northern Ireland (not fluoridated) [Waugh 2014]. High tea consumption (i.e. high Fluoride intake)
showed increased risk of colorectal cancer (RR 1.28 95% CI 1.02-1.61) [Zhang 2010].
 

Oesophagus Cancer

Significantly higher rate of oesophagus cancer was found in fluoridated communities [Takahashi
2001]. The Republic of Ireland (fluoridated) has a higher incidence of oesophagus cancer than
Northern Ireland (not fluoridated) [Waugh 2014]. Generation of HF gas in the stomach is a likely
contributor to increase incidence of this cancer.

Gallbladder Cancer

Significantly higher rate of gallbladder cancer was found for males in fluoridated communities
[Takahashi 2001].

Hodgkin’s Disease

Significantly higher rate of Hodgkin’s Disease was found in fluoridated communities [Takahashi
2001].

Kidney Cancer

Significantly higher rate of kidney cancer was found for females in fluoridated communities
[Takahashi 2001].

Leukaemia

Significantly higher rate of monocytic Leukaemia was found for males in fluoridated US communities
[Takahashi 2001]. The Republic of Ireland (fluoridated) has a higher incidence of Leukaemia than
Northern Ireland (not fluoridated) [Waugh 2014].

Liver Cancer

An increased risk of liver cancer mortality was observed as a function of fluoride concentration in
drinking water Okinawa [Tohyama 1995].
Significantly higher rate of liver cancer was found in fluoridated US communities [Takahashi 2001].
DNA damage, apoptosis and cell cycle changes are induced by fluoride in rat hepatocytes [He 2006].
Significant differences in enzyme systems were observed in liver cancer samples and the ability to
metabolize fluorocarbons [Chen 1997].
Fluoride has been shown to cause lipid peroxidation, DNA damage, and apoptosis in the human
embryo hepatocyte L-02 cell experimental model [Wang 2004].
Human HepG2 cell (perpetual liver cell) DNA damage by Sodium Fluoride (NaF) has been confirmed
[Zhang 2009].
Researchers have investigated Melatonin in treatments that seek to ameliorate liver cancer
induction [Rahman 2003]. As discussed in the present article, Melatonin, a natural cancer defence
mechanism, is depressed Fluoride.

Lung Cancer

Elevated lung cancer was reported for fluorspar miners [Parsons 1964]. Significantly higher rate of
lung cancer was found for males in fluoridated communities [Takahashi 2001]. It has been suggested
that the Fluoride in cigarette smoke might contribute to lung cancer [Sutton 1986].
Hydrogen Fluoride gas is generated in the stomach and can readily be absorbed into the blood.
However there is little recognition in the literature that the HF gas can readily travel through the
airways, destroying tissue wherever it lands. Repeated tissue damage by acid or alkali is a known
cause of cancer.

Lymphoma

Significantly higher rate of Non-Hodgkin lymphoma was found for females in fluoridated
communities [Takahashi 2001]. The Republic of Ireland (fluoridated) has a higher incidence of Non-
Hodgkin lymphoma than Northern Ireland (not fluoridated) and the highest incidence of all 27 EU
members [Waugh 2014].

Myeloma

Significantly higher rate of multiple myeloma was found for women in fluoridated communities
[Takahashi 2001]. Chromosome aberrations were observed in cultured rat bone marrow cells
treated with inorganic fluorides [Khalil 1995].

Nasal and Sinus Cancer

Significantly higher rate of nose and sinus cancer was found for males in fluoridated communities
[Takahashi 2001]. Everyone using fluoridated water for showers, garden irrigation or cleaning inhales
an aerosol of the toxin. In hot communities, some of the aerosol will evaporate to produce Fluoride
nanoparticles that will penetrate to the deepest airways.

Oral Cavity Cancer

Significantly higher rate of larynx, mouth, hypopharynx, nasopharynx, oropharynx and tongue cancer
was found in fluoridated communities [Takahashi 2001]. DNA damage, apoptosis and cell cycle
changes are induced by fluoride in rat oral mucosal cells [He 2006]. Genotoxic oral damage by
Fluoride was observed in human volunteers [Vazquez-Alvarado 2012].

Ovarian Cancer

Significantly higher rate of ovarian cancer was found in fluoridated communities [Takahashi 2001].
This was thought to possibly be associated with the increased levels of gonadotropin, also seen due
to Fluoride intoxication of cryolite workers [Tokar 1977]. Further evidence is the observation that
gonadotropin down-regulates Estrogen receptor-β so that the ratio of Estrogen receptorα/ Estrogen
receptor-β mRNA ratio is altered [Beyers 1997]. A high Estrogen receptor-α/ Estrogen receptorβ
mRNA ratio is associated with increase ovarian cancer malignancy [Pujol 1998].

Pancreatic Cancer

Significantly higher rate of pancreas cancer was found in fluoridated communities [Takahashi 2001].
The Republic of Ireland (fluoridated) has a higher incidence of pancreas cancer than Northern Ireland
(not fluoridated) [Waugh 2014].

Prostate Cancer

Data for 1978-1982 found lower rate of prostate cancer in fluoridated communities [Takahashi
2001]. This was thought to be possibly associated with the depression of testosterone by Fluoride.
However increased hypoxia correlates with increased expression of the angiogenesis marker
vascular endothelial growth factor in human prostate cancer [Cvetkovic 2001, Movsas 2000].
The Republic of Ireland (fluoridated) has a higher incidence of prostate cancer than Northern Ireland
(not fluoridated) [Waugh 2014]. Low teas consumption showed no elevated risk [Ellison 2000],
however evidence of a dose-response increase of prostate cancer with high tea consumption (i.e.
high Fluoride intake) has been found in meta-analysis [Yu 2014, Figure 7].

Skin Cancer

Melanotic tumours were found in test species exposed to Fluoride in 1963 [Herskowitz]. Significantly
lower rate of lip cancer and melanoma was found in fluoridated communities [Takahashi 2001].

Stomach Cancer

Surface changes in rat gastric mucosa are induced by Sodium Fluoride [Easmann, Pashley 1984].
Human volunteers suffered terrible damage to their stomach on ingestion of a single dose of
Fluoride with the lesions taking weeks to heal [Spak 1989].

Testicular Cancer and Progesterone Synthesis

The expression of steroidogenic acute regulatory protein (StAR) mRNA and cytochrome P450
cholesterol side-chain cleavage enzyme (P450scc) mRNA is suppressed in Leydig cells [Guan 2012].

Thyroid Cancer

Significantly lower rate of thyroid cancer was found in fluoridated communities [Takahashi 2001].
Fluoride induces thyroid cell apoptosis [Liu 2014].

Uterus Cancer

An increased risk of uterine cancer mortality was observed as a function of fluoride concentration in
drinking water Okinawa [Tohyama 1996].

Long-lost research linking fluoride to cancer has resurfaced in a Dutch film clip featuring Dr. Dean Burk, who in 1937 cofounded the U.S. National Cancer Institute (NCI) and headed its cytochemistry department for more than 30 years. In the taped interview, he equates water fluoridation to “public murder,” referring to a study that had been done on the 10 largest U.S. cities with fluoridation compared to the 10 largest without it. The study demonstrated that deaths from cancer abruptly rose in as little as a year or two after fluoridation began. This and other studies linking fluoride to cancer were government-ordered but were quickly buried once fluoride was found to be linked to dramatic increases in cancer.

Conclusion

Fluoride is genotoxic and causes cancer via a number of mechanisms. Fluoride directly damages
DNA, affects levels of IGF and related proteins and suppresses Melatonin. Precipitates of Fluoride
doped Hydroxyapatite crystals in various organs have been demonstrated to increase malignancy.
Two fundamental principles must apply:
1] The Precautionary Principle
2] The medical ethic of “Do No Harm”
Consumers should be made aware of the high Fluoride content of tea and associated increased
cancer risk.
Given the overwhelming weight of evidence, continued deliberate exposure of the human
population to Fluoride via fluoridation is criminal negligence.
 
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