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      Growth suppression of four cancer cells by hyperbaric nitrous oxide and methotrexate

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          Abstract

          Background

          Nitrous oxide concentration is easily controlled by respiratory ventilation. It suppresses bone marrow via the inhibition of thymidylate synthesis. The aim of this work was to determine the optimal pressure and exposure duration of nitrous oxide, as well as methotrexate concentration that maximizes the suppression of 4 cancer cells: CCRF-CEM, K562, A549 and MDA-MB-231.

          Methods

          Each cancer cell was cultured in a hyperbaric chamber at 1, 2 and 3 atmosphere of 74% nitrous oxide for 24, 48, and 72 hours at 0, 0.3, 0.7, 1, 2, 5 and 10 µM methotrexate (MTX), respectively. The results were expressed in the ratio of the number of cancer cells cultured under specific conditions (S cells) to that under normal conditions (N cells).

          Results

          The S/N ratio of CCRF-CEM cells was 87.4% in 24-hour culture, 95.0% in 48-hour culture and 115.9% in 72-hour culture (P < 0.05). The S/N ratio of K562 cells was 103.6% at 1 atm, 102.4% at 2 atm and 115.6% at 3 atm (P < 0.05). The S/N ratio of A549 cells was 94.3% at 1 atm, 94.1% at 2 atm, 99.3% at 3 atm, 96.2% in 24-hour culture, 99.2% in 48-hour culture and 99.3% in 72-hour culture (P > 0.05). However, the S/N ratio of MDA-MB 231 cells was 66.9% in 24-hour culture, 83.1% in 48 hour culture and 87.8% in 72-hour culture (P < 0.05).

          Conclusions

          Only the growth of the MDA-MB-231 cells was significantly reduced after a longer exposure time to nitrous oxide, but those of the other cells were not.

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          Most cited references21

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          Vitamin B12, folic acid, and the nervous system.

          There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.
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            Biologic effects of nitrous oxide: a mechanistic and toxicologic review.

            Nitrous oxide is the longest serving member of the anesthesiologist's pharmacologic armamentarium but remains a source of controversy because of fears over its adverse effects. Recently, the Evaluation of Nitrous oxide In a Gas Mixture for Anaesthesia (ENIGMA) trial reported that nitrous oxide use increases postoperative complications; further preclinical reports have suggested that nitrous oxide may contribute to neurocognitive dysfunction in the young and elderly. Therefore, nitrous oxide's longevity in anesthetic practice is under threat. In this article, the authors discuss the evidence for the putative toxicity of nitrous oxide, from either patient or occupational exposure, within the context of the mechanism of nitrous oxide's action. Although it would seem prudent to avoid nitrous oxide in certain vulnerable populations, current evidence in support of a more widespread prescription from clinical practice is unconvincing.
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              Toxicity of nitrous oxide.

              Nitrous oxide interacts with vitamin B12 resulting in selective inhibition of methionine synthase, a key enzyme in methionine and folate metabolism. Thus, nitrous oxide may alter one-carbon and methyl-group transfer most important for DNA, purine and thymidylate synthesis. Long-term exposure to high concentrations of nitrous oxide may cause megaloblastic bone-marrow depression and neurological symptoms. Exposure to higher doses for less than 6 hours, as in clinical anaesthesia, are considered harmless. Recent studies seem to suggest a correlation between nitrous oxide anaesthesia and hyperhomocysteinaemia which is accepted to be an independent risk factor for coronary artery disease. As for today, available data do not support the notion that exposure to trace amounts of nitrous oxide is associated with impaired fertility or an increased risk of developing cancer. Emission of nitrous oxide from medical use is estimated to contribute less than 0.05% to total annual greenhouse gas emission.
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                Author and article information

                Journal
                Korean J Anesthesiol
                KJAE
                Korean Journal of Anesthesiology
                The Korean Society of Anesthesiologists
                2005-6419
                2005-7563
                January 2010
                31 January 2010
                : 58
                : 1
                : 61-69
                Affiliations
                Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Korea.
                [* ]Department of Anesthesiology and Pain Medicine, College of Medicine, University of Ulsan, Seoul, Korea.
                Author notes
                Corresponding author: Wonsik Ahn, M.D., Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, 28, Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea. Tel: 82-2-2072-3087, Fax: 82-2-747-5639, aws@ 123456snu.ac.kr
                Article
                10.4097/kjae.2010.58.1.61
                2872900
                20498814
                8549f702-a70b-4f76-8cad-c64ef314e787
                Copyright © The Korean Society of Anesthesiologists, 2010

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 May 2009
                : 29 August 2009
                : 14 September 2009
                Categories
                Experimental Research Article

                Anesthesiology & Pain management
                methotrexate,nitrous oxide,tumor growth suppression
                Anesthesiology & Pain management
                methotrexate, nitrous oxide, tumor growth suppression

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