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Effects of Opiate on Gene Expressions of Healthy and Cancerous Human Cells-its Implication with Malathion Contamination

Effects of Opiate on Gene Expressions of Healthy and Cancerous Human Cells-its Implication with Malathion Contamination. Caroline Hsiao. A bstract .

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Effects of Opiate on Gene Expressions of Healthy and Cancerous Human Cells-its Implication with Malathion Contamination

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  1. Effects of Opiate on Gene Expressions of Healthy and Cancerous Human Cells-its Implication with Malathion Contamination Caroline Hsiao

  2. Abstract Previous studies have shown that morphine has the capabilities to both promote and inhibit tumor growth. The key factor that establishes the fine line between the two opposite occurrences is the concentration of the morphine being administered. The objective of this study was to determine the differences of the expression of certain genes at low concentrations of morphine in both healthy and cancerous cells. Data from a DNA microarray was analyzed on SpotFire Decision Site to identify the varying expressions of key genes that are involved in nicotinic acetylcholine receptors (nAChR). After healthy white blood cells and U937 cancer cells were exposed to physiological levels of morphine, two of these genes were discovered to be up-regulated in healthy cells and down-regulated in cancer cells, a significant distinction that could lead to implications of cancer detection and possibly alternate treatment. In addition to SpotFire data analysis, a follow-up experiment was conducted to examine the effects of morphine on healthy hemocytes treated with malathion. The results of the experiment showed a significant correlation between Malathion and the control groups when comparing form factor. Further experimentation showed that malathion mimics morphine's effect on hemocytes; this was proven by blocking its effect with Naloxone and L-name. Since opiate and nicotinic signaling systems are very similar in invertebrates and human cells, our results indicate that Malathion may affect tumor development via opiate and nicotinic signaling. The impact of Malathion on environment and human health should be further studied.

  3. Need http://www.vahealth.org/cdpc/CancerPrevention/mortality.htm http://www.nap.edu/openbook.php?record_id=11259&page=8

  4. Knowledge Base: • Morphine: very powerful opiate, used as a painkiller, recently found that human cells produce morphine, morphine may have beneficial affects on certain genes • Malathion: one of the most commonly used organophosphate in the US, is said to be “harmless” but many studies find otherwise • Form Factor: measure of a cell’s roundness over one. • Shows: cell’s activity

  5. Literature Review

  6. Purpose • The purpose of this experiment is to reevaluate the effects of malathion on normal healthy cell form factor • H(a): The form factor of cells treated with Malathion will be significantly higher than that of the control group’s form factor. • H(0): The form factor of cells treated with Malathion will have no statistical difference from control cell form factor. Hypothesis:

  7. Results

  8. Results

  9. Discussion

  10. Conclusion Future Studies

  11. Bibliography Cabello Gertrudis, Valenzuela Mario, VilaxaArnaldo, DuránViviana, Isolde Rudolph, Hrepic Nicolas, and Gloria Calaf; A Rat Mammary Tumor Model Induced by the Organophosphorous Pesticides Parathion and Malathion, Possibly through Acetylcholinesterase Inhibition; Environmental Health Perspectives; vol 109; pgs 471-479; May 2001 Enviormental Toxins. "Cancer Caused By Environmental Toxins."; Web. 15 Sept. 2010. <http://ezinearticles.com/?Cancer-Caused-By-Environmental-Toxins&id=648200>. Ishikawa, M., Tanno, K., Kamo, A., Takayanagi, Y., Sasaki, K., Enhancement of tumor growth by morphine and its possible mechanism in mice;Biological and Pharmaceutical Bulletin, 16, 762-766. George B. Stefano, John D. Burrill, Sergei Labur, Julie Blake, Patrick Cadet; “Regulation of various genes in human leukocytes acutely exposed to morphine: expression microarray analysis”; Med SciMonit; Published: 2005.05.05 George B. Stefano, Richard M. Kream, Kirk J. Mantione, Melinda Sheehan, Patrick Cadet, Wei Zhu, Thomas V. Bilfinger, and Tobias Esch; “Endogenous Morphine/Nitric Oxide-Coupled Regulation of Cellular Physiology and Gene Expression: Implications for Cancer Biology”; Published in June 2008. Gupta, K., Kshirsagar, S., Chang, L, Schwartz, R., Law, PY., Yee, D., Hebbel, RP., Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth [Electronic version]. Cancer Research, 62, 4491-4498. Marilie D. Gammon et. al.; “Enviormental Toxins and Breast Cancer on Long Island. Polycyclic Aromatic Hydrocarbon DNA Adducts”; August 2002; Cancer Epidemiology, Biomarkers & Prevention; Vol. 11; 677–685. Maureen R. Gwinn, Diana L. Whipkey, Lora B. Tennant, and Ainsley Weston; Differential Gene Expression in Normal Human Mammary Epithelial Cells Treated with Malathion Monitored by DNA Microarrays; Environmental Health Perspectives; vol 113; pg 1046-1051; August 2005 Matthew R. Bonner, Joseph Coble, Aaron Blair, Laura E. Beane Freeman, Jane A. Hoppin Dale P. Sandler, and Michael C. R. Alavanja; Malathion Exposure and the Incidence of Cancer in the Agricultural Health Study; American Journal of Epidemiology; Vol. 166; Pgs 1023-1034; May 17, 2007 "UNDERSTANDING ANGIOGENESIS." Angiogenesis Foundation. Web. 17 Sept. 2010. <http://www.angio.org/ua.php>. Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS; Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation; Journal of Biological Chemistry; vol270; pgs 30290-30293; December 22, 1995 Stefano George B., Kream Richard M., Mantione Kirk J., Sheehan Melinda, Cadet Patrick, Zhu Wei, Bilfinger Thomas V., and Esch Tobias; “Endogenous Morphine/Nitric Oxide-Coupled Regulation of Cellular Physiology and Gene Expression: Implications for Cancer Biology”; Semin Cancer Biol; vol 18, pgs 199–210; June 2008 Zhu W, Cadet P, Baggerman G, Mantione KJ, Stefano GB; Human white blood cells synthesize morphine: CYP2D6 modulation; J Immunol; vol 175; pgs 7357-7362; December 2005 Zhu Yu Cheng, Snodgrass Gordon L., Chen Ming Shun; Enhanced esterase gene expression and activity in a Malathion resistant strain of the tarnished plant bug, Lyguslineolaris; Insect Biochemistry and Molecular Biology; vol 34; pgs 1175–1186; May 24 2004

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