Abstract

To the Editor I read the article by Perry et al¹ with interest. Several other molecular mechanisms and factors may also play a role in how anesthesia may influence cancer outcomes. First, it is important to distinguish the difference between certain fluoridated anesthesia, such as sevoflurane, from their contribution to higher plasma fluoride levels. For example, it is known that sevoflurane can provide 20-fold the total daily dietary fluoride intake from all sources of fluoridated food and water combined,² resulting in peak ionic fluoride levels in the range of 50 umol/L.⁴ Hence, fluoridated anesthesia can result in extremely high plasma fluoride levels. Second, it is important to point out that chronic fluoride exposure has been found to decrease the messenger RNA (mRNA) expression of p16 tumor suppressor gene.⁴ Interestingly, a review of published literature will show that loss of p16 predisposes humans to cancer, and p16 inactivation is associated with melanoma, acute lymphocytic leukemia, osteosarcoma, and mesothelioma as well as brain, esophageal, lung, pancreas, bladder, head and neck, breast, ovarian, prostate, and renal carcinoma. However, in addition to downregulating p16, chronic fluoride exposure has been found to upregulate high-sensitivity C-reactive protein, core-binding factor a 1, chemokine (C-C motif) ligand 2, calcitonin, Smoothened mRNA, Sonic Hedgehog signaling pathway, osteoprotegerin, DiGeorge syndrome chromosomal region 8, cyclooxygenases, and prostaglandins E2 expression. Importantly, fluoride exposure has also been shown to be a potent inhibitor of paraoxonase 1 and forkhead box protein 3 transcription factor. A further review of literature will elucidate the significance of these molecular mechanisms in cancer progression and disease outcomes. Furthermore, human studies have also found that chronic fluoride exposure resulting in serum ionic fluoride levels of 3 to 14 umol/L leads to significant inhibition of Na⁺/K⁺–adenosine triphosphatase (NKA) activity.⁵ Here again, a review of literature will show that inhibition of NKA activity is associated with tumor invasiveness, metastasis, and tissue fibrosis as well as kidney, prostate, and bladder cancer. Interestingly, loss of NKA activity is also associated with neurotoxicity, Alzheimer disease, seizures, and mental disorders as well as diabetic nephropathy, cardiomyopathy, and hypertension. Taken together, the molecular mechanisms by which anesthesia may increase the susceptibility to subsequent cancer risk and mortality (in addition to other negative health outcomes) is most likely dependent on the type of inhalation anesthetic used and the effect of excessive fluoride exposure on molecular pathways associated with increased risk of cancer.

Corresponding Author: Declan T. Waugh, BSc, CEnv, MCIWEM, MIEMA, EnviroManagement Services,

• Related Studies :

  • A case-control study of topical and supplemental fluoride use and osteosarcoma risk.

    Background: A relationship between fluoride and osteosarcoma has been hypothesized but not validated. To the authors’ knowledge, there are no published studies examining topical fluoride or dietary fluoride supplements and osteosarcoma risk. The purpose of this study was to examine the association between ever or never use of topical and

  • Environmental Fluoride 1977 by Rose & Marier

    The Associate Committee on Scientific Criteria for Environmental Quality was established by the National Research Council of Canada in response to a mandate provided by the Federal Government to develop scientific guidelines for defining the quality of the environment. The concern of the NRC Associate Committee is strictly with scientific

  • Urinary minerals excretion among primary schoolchildren in Dubai—United Arab Emirates.

    Introduction Urinary excretion of calcium (Ca), magnesium (Mg), phosphorus (P), iodine and fluoride is used to assess their statuses and/or the existence of metabolic abnormalities. In the United Arab Emirates (UAE), the urinary concentration of these minerals among children have not been documented. Materials and methods A cross-sectional study, including 593 subjects (232

  • Evidence-based clinical recommendations regarding fluoride intake from reconstituted infant formula and enamel fluorosis: a report of the American Dental Association Council on Scientific Affairs.

    BACKGROUND: This article presents evidence-based clinical recommendations regarding the intake of fluoride from reconstituted infant formula and its potential association with enamel fluorosis. The recommendations were developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs (CSA). The panel addressed the following question: Is

  • No evidence that fluoride supplements taken during pregnancy prevent caries.

    Data sources: Cochrane Oral Healths Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Medline, Embase, LILACS BIREME Virtual Health Library CINAHL US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform databases. Study selection: Randomised controlled trials (RCTs) including quasi-randomised

• Related FAN Content :

  • Fluoride & Osteosarcoma: A Timeline

    Several human epidemiological studies have found an association between fluoride in drinking water and the occurrence of osteosarcoma (bone cancer) in young males. These studies are consistent with the National Toxicology Program's (NTP) cancer bioassay which found that fluoride-treated male rats had an dose-dependent increase in osteosarcoma. Although a number of studies have failed to detect an association between fluoride and osteosarcoma, none of these studies have measured the risk of fluoride at specific windows in time, which based on recent results, is the critical question with respect to fluoride and osteosarcoma.

  • Fluoride & Liver Cancers in NTP Bioassay

    On October 28, 1988, Battelle Columbus Laboratories submitted its Final Report to the NTP concerning the results of the Mouse study. The principal finding of Battelle's report was that a dose-dependent increase of a rare liver cancer (hepatocholangiocarcinoma) had occurred in the fluoride-treated male and female mice.

  • Fluoride's Mutagenicity: In vivo Studies

    Consistent with dozens of in vitro studies, a number of in vivo studies, in both humans and animals, have found evidence of fluoride-induced genetic damage. In particular, research on humans exposed to high levels of fluoride have found increased levels of "sister chromatid exchange" (SCE). As noted in one study: "In

  • A Critique of Gelberg's Study on Fluoride/Osteosarcoma in New York

    The case-control study by Gelberg, published first as a PhD dissertation and then later in two peer-reviewed journals, may represent the most substantive study on fluoride/osteosarcoma previous to Bassin’s 2001 analysis. In assessing Gelberg’s data, we were at first struck by the existence of several notable errors in both the thesis and papers. While these errors do raise questions about the study, our primary concern with Gelberg’s work relates to the methods she used to analyze her data.

  • Fluoride's Mutagenicity: The "Oral Health Research Institute's" Studies

    Although many in vitro and in vivo studies have detected mutagenic effects from fluoride exposure, the Oral Health Research Institute at Indiana University's School of Dentistry has repeatedly failed to find any such effect in multiple studies on the subject.