By Mats Hanson, Ph.D. Sweden

Some metals are known to be carcinogenic, e.g. chromium and nickel, and others have a protective effect like zinc. magnesium and selenium. Data on mercury are largely lacking. It is quite clear that mercury damages DNA in the same way as x-rays, but the metal is such a potent poison that also the repairing enzymes are damaged. X-ray damage to DNA is rapidly repaired and sometimes errors occur which might cause the cell to become malignant and grow without control. However, mercury damage to DNA is only slightly repaired and the cell will rather die than become malignant (Cantoni et al, 1983). The differences are, however, not absolute and it is not possible to exclude that low levels of mercury will produce DNA damage without affecting the repair enzymes.

A diffent situation exists when tissues have direct contact with metals in concentrated form, e.g. orthopaedic implants (stainless steel containing chromium and/or nickel) and when pieces of metal are implanted into experimental animals. In this situation there is both a toxic effect and a tissue irritation which attracts immune cells. These cells produce free radicals and cytokines which can give both general symptoms and degrade the tissues around the implant. Apparently this is common in orthopaedic surgery where something called "aseptic loosening" occurs and the surgeon has to reoperate. In the surgical literature there is a discussion whether this is a cancer risk.

Mercury suspected

Mercury is on the "suspect list" for being carcinogenic and a study often cited when discussing this question is a report by Druckrey et al.. (1957). They injected 0.05 ml metallic mercury into the abdominal cavity of rats twice during fourteen days. Poisoning symptoms appeared in most animals after some time but disappeared after a few months. Cancer developed in 5 of 12 animals (spindle cell sarcoma), starting after 22 months. Inside each tumor there was a drop of mercury in a cavity of degraded tissue. Cancer only appeared in places where there was a direct contact with the metal and not in tissues where mercury had accumulated in high concentrations (i.e. kidneys).

Mercury in jaw tissue

A similar situation exists in the oral cavity. Amalgam with 50 % mercury often has direct contact with the buccal mucosa, the tongue and sometimes with the gingival margin. Pieces of amalgam are sometimes found in the soft or hard tissues and there are cases where small drops of mercury have been found. In addition to direct toxic effects there are also electrochemical ones. The exposed surface of the metal filling will form the cathode in a battery and the hidden surfaces the anode. The battery is driven by the difference in oxygen availability. The electrochemic dissolution of metals takes place at the anodic surface where also hydrochloric acid is formed. At the cathodic surface, however, sodium hydroxide is formed. Caustic soda is, as everyone knows, corrosive. The hydroxide can also form on gold surfaces, especially if amalgam is present underneath.

Leukoplakia

Inflammations, ulcers and tissue changes in the mouth have changed names since the 19th century and today the similar tissue-changes have different names in different countries. Early denominations were stomatitis, gingivitis etc; they are still sometimes used. In the USA a popular diagnosis is leukoplakia with various additional names. Leukoplakia is characterized by a generally smooth, thin, white appearance. The "smoothness" applies both to color and appearance. If the changes have other appearances they are called "non-homogenous leukoplakia" and comprise various changes which are might be called something quite different by dentists in other countries. From the literature it appears that dentists i each country have rather similar diagnostic criteria.

Leukoplakia is generally regarded as a precancerous change and estimates of the percentage of malignant transformations varies from a few % to 34 % (Bouquot et al, 1986). This latter study seems to be one of the largest and most thorough. Out of 23616 examined persons in Minnesota, USA, 3,38 % (798 cases) had changes which were classified as: leukoplakia 2,89 %; tobacco-related 0,23; chronic cheek biting 0,12; lichen planus 0,11; leukoedema 0,03. Within the leukoplakia-group 44 cases of cancer or severe dysplasia appeared (0,2% of all examined). The study should be representative for USA och western Europe even if it is likely that many leukoplakia cases would have been classified differently in many european countries.

Pathological changes in the mouth

Lain & Caughron (1936) were among the first to notice the connection between dental fillings, especially combinations of gold and amalgam, and pathological changes in the mouth. They noted:
"Mucosa. - In examination of the mucosa, there are found: (1) erythema with congestion and blanching of the mucosa, and evidence of intermittent or chronic irritation; (2) prominence and sensitivity of both anterior and posterior groups of the papillary bodies of the tongue; (3) erosion areas and ulcers on the margins, and denuded patches, geographic linguae, on the dorsal areas of the tongue, even the more severe symptoms being periodic and influenced by a change in diet, and (4) leukoplakia, a grayish, slightly elevated, precancerous lesion, usually resulting from a long period of chronic irritation, which may be nature's warning before more serious pathologic processes develop.

Electrochemical effect

Electrogalvanic lesions upon the mucosa most frequently occur adjacent to or near the positive metal, though some times occurring elsewhere . . . . . Positive cases of electrogalvanism will begin to improve at once and all lesions except leukoplakia, which is a hypertrophy of tissue, will heal promptly after the removal of prostheses of either the positive or the negative group. When lesions have healed, new restorations made with perfectly homogeneous metals are a guarantee against recurrence". (Lain & Caughron, 1936)

There are a number of case reports of leukoplakia in direct connection with combinations of metals, usually gold and amalgam. Leukoplakia is a serious condition as Lain & Caughron pointed out, but there are cases where the tissue changes have healed after the metals have been removed (Schmitt 1955; Inovay & Bonoczy 1961; Lind et al 1984).

Lichen

In Sweden and Europe the most common diagnosis seems to be lichen with various sub-names, e.g. reticular (like a net of white, hardened stria) , atrofic form with reddish, inflamed tissue and erosive form with ulcers.

Some oral pathologists try to distinguish between lichen adjacent to metal fillings and more extensive tissue changes. They claim, on very thin evidence, that the causes are different (metal allergy and unknown, resp.). Histologically there is no difference. All lichen changes are characterized by a hardened mucosal surface, a subsurface layer of cells in various stages of dissolution and a massive accumulation of immune cells, mainly T-cells with some contribution of other cells.

A Medline search (search terms: oral lichen; cancer, 1980-2001) shows that the vast majority of publications consider lichen to be a potentially precancerous lesion. A number of studies have followed-up patients with lichen and find that one to a few percent become malignant within 10-15 years (Dunsche & Harle 2000). Lichen is often symtom-free, except when ulcers develop, and the condition arouses no suspicion in the patient. The dentist, when he notices such changes, should take a biopsy and send to a pathological laboratory and then follow-up and examine the patient regularly. Experience by swedish amalgam patients indicate that you can have lichen for years without any dentist reacting. The prevalence of lichen in the population is 0,5-2,2 % (Setterfield et al 1985). 0,4 to 12,5 % of these develop into cancer. (Holmstrup et al 1992; Lo Muzio et al 1998). Several other studies draw the same conclusion and show that about one to a few % become malignant in european populations. The range of results are likely caused by the rather low number of patients in each study.

Relationship between lichen and dental fillings

Few studies attempt to explain the causes of the oral changes. Studies from Sweden constitute an exception where a connection between dental rerstorative materials and lichen has been clearly stated.
Abroad the blinds seem to be massive. When you look up the relevant literature (without blinds) you are immediately struck by the localization of the damage. Direct impressions of amalgam (or gold on top of amalgam) on the mucosa with the most severe changes in the contact area and streaks of lichen radiating from this central area are often visible (Silverman et al, 1985). When the Swedish Association of Dental Mercury Patients (Tf) started (1978) there was a booklet called "Tumors in the oral cavity", published 1966 by the Swedish Dental Association in collaboration with the Cancer Society, containing "nice" pictures in color of lichen and cancer directly in contact with ugly, corroding fillings. When our patient organisation asked for additional copies of the booklet it was suddenly withdrawn "after consultations with dental experts"!

In the booklet, mentioned above, "chronic irritation of a mechanical or chemical nature" is mentioned as a predisposing factor. In some other studies tobacco and alcohol use/abuse has also shown an association with higher risk and in some studies from Southeast Asia, betel chewing. Fruit and vegetables and antioxidant vitamins provide protection; especially beta-carotene has shown a positive effect.

A. Larsson, professor of oral pathology in Malmo, Sweden, writes that the majority of all lichen-biopsies (10-15 % of all biopsies, ca 4500/year) appear to be clinically associated with metal fillings, primarily amalgam. Further that the research literature does not appear to be especially interesested in publishing studies on the relations to contact with metals in the oral cavity (Larsson, 1998). However, there are a number of papers describing the effects of amalgam removal on lichen lesions. Lichen, often ulcerated, disappears rapidly if amalgam in direct contact with the lesion is removed (James, 1987; Laine et al, 1992; Pang & Freeman,1995; Koch & Bahmer, 1995; Smart et al ,1995; Ibbotson et al,1996). Patch tests for mercury allergy is meaningless. Patients with amalgam-associated lichen show much more often a positive skin reaction compared to lichen-patients without direct contact between the lesions and oral metals or the general population, but at least half of them are anyhow negative. Regardless of the patch test reaction, lichen in contact with amalgam disappears when the metals are removed. It is not possible to predict in advance who should benefit from amalgam removal, based on results from patch tests (Skoglund, 1994; Henriksson et al, 1995).

In the dental literature on lichen and amalgam it is often stated that lichen in contact with amalgam is likely caused by toxic effects/allergy, but that more extensive lichen, even if it is confluent with the contact area to amalgam, is likely caused by something else, unknown. This opinion is presumed to be supported by the fact that patients with lesions in contact with metals more often show a positive patch test reaction and that the contact lesions heal quickly after metal removal whereas more extended tissue changes heal slowly or not at all. Nobody gives a thought to the possibility that lichen might not appear at all, or only rarely, if toxic substances were not used in dentistry.

Also lichen without amalgam contact disappear or improves if amalgam is removed (Henriksson, 1995; Östman et al, 1996; Bolewska, 1990), but much more slowly. Obviously the choice of replacement material must be of utmost importance. From some studies it appears that metal-bound porcelain is just as bad as amalgam (Larsson & Warfvinge, 1995; Hensten-Pettersen, 1998). In one study the treatment consisted of polishing the amlgam fillings, something which did not help at all (Buser et al, 1992). I phoned some of "our dentists" and they confirm that also lichen, without direct amalgam contact, slowly improves if amalgam, gold+amalgam or metal-bound porcelain is replaced with materials which usually do not cause problems (some composites, ceramics). Gold alloys, used today, contain platinum or palladium, and are generally not usable alternatives. An additional factor which might be of importance for the absorption of metals has been pointed out by Larsson: the use of sodium laurylsulfate in nearly all tooth pastes. Lauryl sulfate is a detergent (soap) which enhances the sensitivity of oral tissues in experimental animals to mercury and tin but not copper (Larsson et al, 1990). However, mercury is readily absorbed also by intact mucosa (Bolewska et al, 1990) and is found at high levels in the oral tissues in persons with amalgam fillings (Willershausen-Zönnchen, et al, 1992).

Provocation of the immune system

The varying reactions with and without direct amalgam contact are readily explainable without speculation on different causes. The type of immune reaction depends on the level of mercury, individual sensitivity and the degree of provocation of the immune system. Children, poisoned by mercury in teething powders or worm medicines (acrodynia) rarely showed a positive skin reaction on patch tests, despite that the disease was generally considered to be an allergic reaction. Some children had a positive patch test reaction when they were most severely ill, but a negative one a few weeks later. Some children, by mistake, got an additional exposure from swallowed mercury (calomel) and then previously negative patch test areas on the skin suddenly flared up (Fanconi,1947). If amalgam in contact with the oral mucosa is removed, the extremely high mercury levels in the contact area will rapidly diminish by diffusion. The further reduction of mercury levels in this area and generally in the mouth will follow an exponential curve which means that lower levels of metal will remain in the tissues for a long time and only slowly decline. These levels might very well be sufficient to sustain local immune reactions in more extended lesions.

Avoidance of the problem

A general impression from the literature is that the authors in every way try to avoid the problem that metals, especially amalgam, causes damage to oral tissues, damage which in some cases lead to cancer. Those who recognize the problem try to minimize it by using more or less strange explanations that limit the casual association to amalgam for only contact lesions. Swedish dental researchers seem to have been most outspoken. However, also in the swedish dental literature there are amazing speculations that patients with lichen exhibit a "depression-prone personality" and "when they are exposed to stressful life events, a depression might develop but is masked and somatized as an OLR" (oral lichenoid reaction). (Östman et al, 1996).

Mercury is corrosive

Oral ulcers and inflammations belong to the classiscal symtoms of mercury poisoning, irrespective of amalgam in the teeth. Direct contact with high levels of mercuric chloride is directly corrosive; mercuric chloride has since old times been called corosive sublimate. Mercury is immunotoxic and induces immune dysregulation. Cells from human oral mucosa which are exposed to HgCl2 in vitro at much lower levels than those present i oral tissues (from amalgam), are stimulated to express a surface protein, called ICAM-1. The protein attracts and activates T-cells which in turn produce a number of cytokines which are directly inflammatory and tissue degrading (Little et al, 2001). Skin cells of the same type do not react in the same way. The mechanism is sufficient to explain the development of lichen and other inflammatory changes, also in mucosa without direct amalgam contact.

The article war first published in TF-Bladet (Journal of the Swedish Association of Dental Mercury Victims) No. 3, 2001

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