Excerpt from:

Fluoride: The Aging Factor (2nd Edition)
Author: Dr. John Yiamouyiannis
Published: Health Action Press
Year: 1986 (first edition 1983, third edition 1993)
ISBN: 0-913571-01-6

(To order a copy of "Fluoride: The Aging Factor" from Amazon click here. If Amazon is out of stock, you can order a copy at http://www.nutech2000.com.au/prod3.htm.)

About the Author: Dr. John Yiamouyiannis was, until his passing in the fall of 2000, the world's leading authority on the biological effects of fluoride. His formal education included a B.S. in biochemistry from the University of Chicago and a Ph.D in biochemistry from the University of Rhode Island. After a year of postdoctoral research at Western Reserve University Medical School, Yiamouyiannis went on to become biochemical editor at Chemical Abstracts Service, the world's largest chemical information center. It was at Chemical Abstracts Service, where Yiamouyiannis became interested in the damaging effects of fluoride.

Chapter 8: Fluoride & Genetic Damage

As pointed out in Chapter 4, all animals, including humans, are made up of cells. Each cell contains a nucleus, which is separated from the remainder of the cell by a nuclear membrane. Within the nucleus exist chromosomes, which contain DNA and protein. DNA is the body's master blueprint material. It is the genetic material that determines how the body is built. DNA specifies traits such as height, hair texture and color, number of fingers on each hand, blood type, and by means of its control of protein and enzyme synthesis, the susceptibility of the individual to various diseases.

Since maintaining the integrity of this master blueprint is so vital, the cell makes a "photocopy" of the DNA called RNA, so that the risk of damaging the DNA is minimized. This photocopy blueprint is taken to "construction sites" in the cell. These construction sites are called ribosomes. On these ribosomes, the RNA blueprint is used to direct the manufacture of proteins and enzymes, which, in turn, directly determine the structure, traits, and limiting capabilities of the body.

To further insure the integrity of DNA, the cell provides a group of enzymes called the DNA repair enzyme system which repairs DNA when damage is done to it. As people age, their DNA repair enzyme system slows down. This results in DNA damage which goes unrepaired and leads to cell damage or death. Damaged or dead cells may then put out products which in turn damage other cells, leading eventually to massive cell death and the degenerative loss of various tissues and organs in a snowballing cycle of aging > damage > aging ....

Serious consequences can also arise if the unrepaired DNA damage occurs in a cell which gives rise to a sperm or egg cell. In these cases, DNA damage in the defective egg or sperm cell will be replicated in every cell of the offspring's body and will lead to a birth defect. If the child with this birth defect survives to maturity and reproduces, this genetic deformity will be passed on from generation to generation. A decline in DNA repair activity with "age" is one of the reasons why the number of birth defects increases as maternal age increases.

Unrepaired damage of a segment of the DNA responsible for control of cell growth (brought about by a deficient DNA repair enzyme system) can lead to uncontrolled cell growth or tumors. Many tumors stop growing when they are contained by the cells around them. However, in some cases, tumor cells may release an enzyme, or may be induced by additional genetic damage to release an enzyme, which digests the surrounding cells. The result is an invasive or malignant tumor and is more commonly referred to as cancer.

An excellent example of a defective DNA repair enzyme system leading to cancer is provided by victims of a disease called xeroderma pigmentosum. These people suffer from an inherited deficiency of DNA repair enzyme activity and are known to succumb to cancer early in life as a result.

A decline in DNA repair activity with "age" is one of the primary reasons why the incidence of cancer among older people is so much higher than the cancer incidence among younger people. The defective DNA repair enzyme in patients with xeroderma pigmentosum accelerates the aging process to the extent that xeroderma pigmentosum patients in their 20's have the same cancer risk as "normal" people in their 80's.

Dr. Wolfgang Klein and co-workers at the Seibersdorf Research Center in Austria reported that 1 part per million fluoride inhibits DNA repair enzyme activity by 50%. Since fluoride inhibits DNA repair enzyme activity, fluoride should also be expected to lead to an increase in genetic or chromosome damage.

This has indeed been found to occur in numerous studies showing that fluoride in water, even at the concentration of 1 part per million, can cause chromosome damage.

The following table outlines the results of laboratory studies regarding the effect of fluoride on genetic damage in mammals.

*A prepublication copy of this paper was submitted as an exhibit in a court case in Pittsburgh (USA). During trial, it was brought out that the results showed that increasing fluoride contents in drinking water increased genetic damage in mouse testes cells. Before the paper was published these figures were altered so as to destroy the original figures showing a relation between fluoride and genetic damage (see Chapter 16).

One of the most relevant of these studies are those of Dr. Aly Mohamed, a geneticist at the University of Missouri. They show that one part per million fluoride in the drinking water of mice causes chromosomal damage. These studies also show that as the fluoride content of the water increases the degree of chromosomal damage increases in both testes and bone marrow. The results are presented in the following table:

(Click to enlarge table)

Chromosomes (and thus any chromosomal abnormalities that may occur) are only visible while the cell is dividing. Therefore, Dr. Mohamed studied bone marrow and testes cells since these cells divide rapidly.

Since the testes cells observed by Dr. Mohamed give rise to sperm cells which are passed on to future generations, genetic damage to these testes cells can lead to birth defects and other metabolic disorders which can be passed on from generation to generation.

Early studies regarding the ability of fluoride to cause chromosome damage were done on plants and insects and as a result drew little attention. However, since the basic structure, function, and repair of chromosomes is similar in plants, insects, and animals, substances like fluoride which cause genetic damage in plants and insects, will most likely cause genetic damage in animals-including man.

The following table outlines the results of laboratory studies regarding the effect of fluoride on genetic damage in plants and insects.

Drs. R.N. Mukherjee and F.H. Sobels from the University of Leiden in Holland found that fluoride increased the frequency of genetic damage in sperm cells which were produced by laboratory animals exposed to X-rays. It is evident, from their studies, that fluoride inhibited the repair of DNA damaged X-rays. The authors themselves concluded: "sodium fluoride resulted in a consistent and highly significant increase of the mutation [i.e. genetic damage] frequency. This effect is thought to result from interference with a repair process."

In agreement with Drs. Mukheijee and Sobels were Dr. S.I. Voroshilin and co-workers from the Russian Research Institute of Industrial Health and Occupational Diseases. From their studies they concluded: "It would seem to us that fluoride could cause some kind of disturbance in the enzymes that are related to the mechanisms of DNA repair and synthesis."

In 1981, Dr. A. Iarez and co-workers from the Department of Toxicology from Central University ofVenezuela in Caracas, reported that fluoride added to the drinking water of female rats produced birth defects in their offspring. Just one year later Drs. Rhuitao Zhang and Shunguang Zhang of the Changjian Institute of Marine Products found that fluoride caused birth defects in fish.

According to the June 16, 1976 issue of the San Diego Union, an experiment showed that 10% of the litters of female mice drinking tap water from Durham, North Carolina (fluoridated in 1962) contained at least one malformed baby. No birth defects were observed in mice drinking purified water. While this study in itself does not prove that fluoride was the cause, the effects of fluoride as determined by the investigators mentioned above certainly make fluoride a prime suspect.

Fluoride-Induced Cancer

The ability of fluoride to cause genetic damage is so well recognized that investigators are now trying to find ways to counteract its genetic damaging effects.

Substances like fluoride which cause genetic damage are called mutagenic substances and it is a well-accepted fact that substances which are mutagenic also tend to be carcinogenic, or cancer producing. In fact, this is exactly what has been found with regard to fluoride.

Dr. Takeki Tsutsui and co-workers of the Nippon Dental College in Japan showed that fluoride not only caused genetic damage but was also capable of transforming normal cells into cancer cells. The levels of fluoride used in this study were the same levels of fluoride that the U.S. National Cancer Institute suggested should be used to determine whether or not fluoridation of public water supplies causes cancer.

They found that cells treated with 34 and 45 parts per million fluoride produced cancer (fibrosarcoma) when injected under the skin of otherwise healthy adult hamsters. In contrast, they found that cells that were not treated with fluoride did not produce cancer.

This confirms the earlier U.S. National Cancer Institute sponsored studies done by Drs. Irwin Herskowitz and Isabel Norton. In 1963, these St. Louis University scientists showed that low levels of fluoride increased the incidence of melanotic tumors in fruit flies by 12 to 100% (see the following figure).

(Click here to enlarge)

Similar types of transformations of normal cells to potentially cancerous cells have been observed in humans.

Dr. Danuta Jachimczak and co-workers from the Pomeranian Medical Academy in Poland reported that as little as 0.6 part per million fluoride produces chromosomal damage in human white blood cells. This study has received support from two other studies by Dr. R. Lin and co-workers from the Kumming Institute of Zoology and Dr. E.J. Thomson and co-workers from the Medical Research Council in Edinburgh, Scotland, who showed a 2-fold to 15-fold increase in chromosomal aberration rates at levels of 1.5 to 60 parts per million fluoride. The Thomson study suffers from the fact that the investigators administered another mutagenic substance to all the cells tested to measure other indexes of chromosomal activity.

Dr. Stephen Greenberg from the Chicago Medical School observed a disturbance of the DNA in white blood cells of animals treated with 5-10 ppm fluoride and observed other changes which he maintained were characteristic of cancer cells. In humans, Dr. Paul H. Duffey and co-workers from the Tucson Medical Center also found that fluoride transforms certain white blood cells into cells which appeared to be cancerous.

It is quite clear that fluoride causes genetic damage. The mechanism of action of fluoride cannot be exactly pinpointed because fluoride interferes with a number of physiological processes. Most evidence indicates that fluoride acts on the DNA repair enzyme system. This does not rule out the possibility that fluoride also interferes with DNA synthesis or that it may even act directly on the DNA itself. DNA is composed of two molecular strands held together by hydrogen bonds and fluoride is capable of disrupting these bonds. Such disruption would be expected to result in genetic damage directly and/or interference with DNA synthesis and DNA repair.

Furthermore, fluoride-induced genetic damage may also result from the general metabolic imbalance caused by fluoride selectively inhibiting certain enzymes.

The fact that fluoride has also been shown to cause cancer should not be surprising since it is almost universally accepted that cancer results from genetic damage.

In any event, the fact that fluoride disrupts DNA repair enzyme activity, the fact that fluoride causes genetic damage, and the fact that fluoride causes cancer shows again that fluoride is directly accelerating the aging process.

REFERENCES:

John Little, "Relationship Between DNA Repair Capacity and Cellular Aging," Gerontology, Volume 22, pp. 28-55 (1976).

Wolfgang Klein, et al., "DNA Repair and Environmental Substances," Zeitschrift fur AngewanilteRader und Klimaheilkunde, Volume 24, No. 3, pp. 218-223 (1977).

Wolfgang Klein, et al., "Biochemical Research on the Action of Sodium Fluoride on Mammalian Cells. The Effect on Biosynthesis of Nucleic Acid and Proteins on Mouse Spleen Cells in in Vivo Studies," Report ofthe Austrian Society of Atomic Energy, Seibersdorf Research Center, No. 2355, pp. 1-10 (1974).

Wolgang Klein, et al., "DNA Repair and Environmental Substances," Report of the Austrian Society of Atomic Energy, SeibersdorfResearch Center, No. 2613, pp. 1-9 (1976).

S.I. Voroshilin, et al., "Cytogenetic Effect of Inorganic Fluorine Compounds on Human and Animal Cells in Vivo and in Vitro," Genetika, Volume 9, No. 4, pp. 115-120 (1973).

Georgiana Jagiello and Ja-Shein Lin, "Sodium Fluoride as Potential Mutagen in Mammalian Eggs," Archives of Environmental Health, Volume 29, pp. 230-235(1974).

Danuta Jachimczak and Bogumila Skotarczak, "The Effect of Fluorine and Lead Ions on the Chromosomes of Human Leucocytes in Vitro." Genetica Polonica, Volume 19, No. 3, pp. 353-357 (1978).

George Martin, et al., "Lack of Cytogenetic Effect in Mice or Mutations in Salmonella Receiving Sodium Fluoride," Mutation Research, Volume 66, pp. 159-167 (1979).

A.A. Aliev and D.A.Babaev, "Cytogenetic Activity of Vitamins in Bone Marrow Cells of Rat Femurs in Sodium Fluoride-Induced Mutation Conditions," Tsitol. Genet., Volume 15, pp. 19-23 (1981).

A.A. Aliev, et al., "Effect of alpha-Ibeopherol on the Level of Chromosome Aberrations Induced by Sodium Fluoride in Rat Femur Bone Marrow Cells," Izv. Akad. Nauk Az. SSR Ser. Biol. Nauk., No. 1, pp. 17-20 (1981).

V. Yu Akhundov, et al., "Effect of Combined and Separate Exogenous Vitamin Administration on the Level of Chromosomal Aberrations Induced by Sodium Fluoride in Rats in Subacute Experiments," Izv. Akad. Nauk Az. SSR, Ser. Biol. Nauk, No. 4, pp. 3-5 (1981).

Aly Mohamed and M.E. Chandler, "Cytological Effects of Sodium Fluoride on Mice," Fluoride, Volume 15, No. 3, pp. 110-118 (1982).

Weishun He, et al., "Effect of Sodium Fluoride and Fluoroacetamide on Sister Chromatid Exchanges and Chromosome Aberrations in Cultured Red Muntjac Cells," Huanjing Kexue Xuebao, Volume 3, pp. 94-100 (1983).

Takeki Tsutsui, et al., "Sodium Fluoride-induced Morphological and Neoplastic T~ansfbrmation, Chromosome Aberrations, Sister Chromatid Exchanges, and Unscheduled DNA Synthesis in Cultured Syrian Hamster Embryo Cells," Cancer Research, Volume 44, pp. 938-941 (1984).

Thkeki Tsutsui, et al., "Cytotoxicity, Chromosome Aberrations and Unscheduled DNA Synthesis in Cultured Human Diploid Fibroblasts Induced by Sodium Fluoride," Mutation Research, Volume 139, pp. 193-198 (1984).

A.H. Mohamed, et al., "Cytological Reactions Induced by Sodium Fluoride in Allium Cepa Root-Tip Chromosomes," Canadian Journal of Genetics and Cytology, Volume 8, pp. 241-244 (1966).'

A.H. Mohamed, et al., "Cytological Effects on Hydrogen Fluoride on 'Ibmato Chromosomes," Canadian Journal of Genetics and Cytology, Volume 8, pp. 575-583 (1966).

A.H. Mohamed, "Cytogenetic Effects of Hydrogen Fluoride Treatment in `Ibmato Plants," Journal of the Air Pollution Control Association, Volume 18, pp. 395-398 (1968).

A.H. Mohamed, "Chromosome Changes in Maize Induced by Fluorine Gas," CanadianJournal ofGenetics andCytology, Volume 12,pp. 614-620(1970).

A.H. Mohamed, "Induced Recessive Lethals in Second Chromosomes in Drosophila Melanogaster by Hydrogen Fluoride," Proceedings of the Second International Clean Air Congress of the International Union ofAir Pollution Prevention Associations, 1970, p. 26.

R.A. Gerdes, et al., "The Effects of Atmospheric Hydrogen Fluoride upon Drosophila Melanogaster," Atmospheric Environ., Volume 5, pp. 113-122 (1971).

B. Mitchell and R.A. Gerdes, "Mutagenic Effects of Sodium Fluoride and Stannous Fluoride on Drosophila Melanogaster," Fluoride, Volume 6, pp. 113-117 (1973).

E. Vogel, "Strong Antimutagenic Effects of Fluoride on Mutation Induction by Trenimon and 1-Phenyl-3, 3-Dimethyltriazene in Drosophila Melanogaster," Mutation Research, Volume 20, pp. 339-352 (1973).

S.S. Bale and G.E. Hart, "Cytogenetic and Genetic Effects of Fluoride on Barley. I. Comparative Study of the Effects of Sodium Fluoride and Hydrofluoric Acid on Seedling Root Tips," Canadian Journal of Genetics and Cytology, Volume 15, pp. 695-702 (1973).

S.S. Bale and G.E. Hart, "Cytogenetic and Genetic Effects of Fluoride on Barley. IL Effects of Treatments of Seedling Coleoptiles with Sodium Fluoride," Canadian Journal of Genetics and Cytology, Volume 15, pp. 703712(1973).

A.A. Aliev, et al., "Cytogenetic Effect of Sodium Fluoride Treatment ofAllium Fistulosurn L. Seeds," Izv. Akad. Nauk Az. SSR, Ser. Biol. Nauk, No. 2, pp. 8-10 (1982).

G.K. Ragamova, et al., "Features of the Modifying Capacity of Mutations in Aegilops Seed Produced Under Various Ecological Conditions," Izv. Akad. Nauk Az. SSR, Ser. Biol. Nauk, No. 4, pp. 21-24 (1983).

R.N. Mukheijee and F.H. Sobels, "Me Effect of Sodium Fluoride and Iodoacetamide on Mutation Induction by X-Irradiation in Mature Spermatozoa of Drosophila," Mutation Research, Volume 6, pp. 217-225 (1968).

A. larez, et al., "Sodium Fluoride, Fetotoxicity, and Oral Experimental Teratogeny in Rats," Thricological Aspects [9th Annual Symposium of the International Congress of the European Association of Poison Control Centers], 1981, pp. 528-540.

Ruitao Zhang and Shunguang Zhang, "Ibxicity of Fluoride to Fish," Huangjing Kexue, Volume 3, pp. 1-5 (1983).

Irwin Herskowitz & Isabel Norton, "Increased Incidence of Melanotic Tumors in Two Strains of Drosophila Melanogaster Following Treatment with Sodium Fluoride," Genetics, Volume 48, pp. 307-310 (1963).

Danuta Jachimzcak and Bogumila Skotarczak, "The Effect of Fluorine and Lead Ions on the Chromosomes of Human Leucocytes in Vitro," Genetica Polonica, Volume 19, No. 3, pp. 353-357 (1978).

Stephen Greenberg, "The Reaction of Mouse Leukocytes to Long-Term Fluoride Exposure," Anatomical Record, Volume 196, No. 2, pp. 266-267 (1980).

Stephen Greenberg, "Leukocyte Response in Young Mice Chronically Exposed to Fluoride," Fluoride, Volume 15, No. 3, pp. 119-123 (1982).

Paul Duffey, et al., "Giant Cells in Bone Marrows of Patients on High-Dose Fluoride Treatment," Annals of Internal Medicine, Volume 75, pp. 745--747 (1971).

Listed below are some additional related references:

Nobutake Kanematsu, "Genetic Toxicity of Biomaterial. DNA Damaging Effects of Sodium Fluoride and Other Fluoride Compounds," Japanese Journal of Oral Biology, Volume 27, pp. 372-374 (1985).

V. Ya. Nikiforova, "Mechanism of the Mutagenic Action of Fluoride," Tsitol. Genet., Volume 16, pp. 40-42 (1982).

L.S. Strochkova, et al., "Effect of Fluoride on Morphological and Metabolic Modifications in Hela Cell Culture," Tsitologiya, Volume 26, pp. 299-306 (1984).

Thshio Imai, et al., "Effects of Fluoride on Cell Growth of Two Human Cell Lines and on DNA and Protein Synthesis in Hela Cells," Acta Pharmacol. 7bxicol., Volume 52, pp. 8-11 (1983).

Kataoka Masayuki, "Effect of Sodium Fluoride on Blastogenesis in Mouse Lymphocytes with Special Reference to the Uptake on 3H-Thymidine, 3 H-Uridine, or 'H-Leucine," Shika Gakuho, Volume 84, pp. 229-251 (1984).

Chong Chang, "Effect of Fluoride on Nucleotides and Ribonucleic Acid In Germinating Corn Seedling Roots," Plant Physiology, Volume 43, No. 5, pp. 669-674 (1968).

V.I. Shepotinovsky and Z.I. Mikashinovich, "Metabolic Response of Leukocytes as an Indicator of Animal Individual Reaction to Stress and Injury-Induced Shock,"Byull. Eksp. Biol. Med., Volume 90, No. 10, pp. 420-422 (1980).

Armando Moucdcy, "Histochemical (Glycogen, RNA, and Lipids) Studies of the Liver Cells of Rats Treated with Potable Water Containing Sodium Fluoride in Various Concentrations," Rev. Fac. Odontol. Univ. Sao Paulo, Volume 6, No. 3, pp. 197-215 (1968).

George Waldbott, et al., "Genetic Damage, Birth Defects, and Cancer," in Fluoridation: the Great Dilemma, Coronado Press, 1978, pp. 209-238.

John Remington Graham and Dean Burk, "Editorial Essay," Fluoride, Volume 17, pp. 63-69 (1984).