Study was amid to detect some trace elements in human tumor tissue, Manganese, cobalt, cadmium and Zink was measured in cancer and benign  tissue using atomic absorption ,  result show that cancer tissue have higher concentration of cobalt and Zink than  benign tissue,  it were 156.7±6.5 and 205.79 µg\g respectively. females had higher concentrations  than males in cancer 2011.41±439.79, 114..54±0.05, 157.05±6.50 206.58±20.93 µg\g in Mn, Cd , Co and Zn respectively also in benign tissue Female 2373.37±703.56, 114.56±0.06, 154.50±29.4, 204.65±28.23 µg\g in the same minerals above. Keywords:  trace elements, atomic absorption, tumors tissue

Abed-Neama, Zahraa

AL –Mamoori, Ayad M.J.

al-kilabi, liwaa Hussein

Al-Saadi, Ali Hmood

Al-Terehi, Mona

Zaidan, Haider K.

English

International Institute for Science, Technology and Education (IISTE): E-Journals

Journal of Pharmacy and Alternative Medicine                                                                                                                                 www.iiste.org ISSN 2222-4807 (online) ISSN 2222-5668 (Paper) An International Peer-reviewed Journal Vol.6, 2015  34 Heavy Metals Concentration Detection in Tumor Tissue   Mona Al-Terehi1      liwaa Hussein al-kilabi2      Zahraa Abed-Neama4      Ayad M.J. AL –Mamoori3 Ali Hmood Al-Saadi3      Haider K. Zaidan3 1.University of Kufa, College of Scienc 2. University of Kufa college of medicine 3.University of Babylon, College of Science 4.Al-QAdesia University- College of Science  Abstract  Study was amid to detect some trace elements in human tumor tissue, Manganese, cobalt, cadmium and Zink was measured in cancer and benign  tissue using atomic absorption ,  result show that cancer tissue have higher concentration of cobalt and Zink than  benign tissue,  it were 156.7±6.5 and 205.79 µg\g respectively. females had higher concentrations  than males in cancer 2011.41±439.79, 114..54±0.05, 157.05±6.50 206.58±20.93 µg\g in Mn, Cd , Co and Zn respectively also in benign tissue Female 2373.37±703.56, 114.56±0.06, 154.50±29.4, 204.65±28.23 µg\g in the same minerals above. Keywords:  trace elements, atomic absorption, tumors tissue.        Introduction  As a results of contamination in Iraqi environment which increased after wars and used different weapons, trace elements were increased in different sites; soil, water, food and air, thus present study was suggested to detection some trace elements in human tumors tissue. Different study in Iraqi environment improved increasing in minerals concentration in different site such as air, soil, river water and plants in another hands other studies suggested these minerals roles in carcinogenicity and cytotoxicity on human body. Taha et al., (2005) improved that the concentration of some minerals in the air of districts in Hilla city was abnormally high,. also many local studies explained the high concentrations of these metals in the local environment (air, water and food). Cadmium (Cd) an known  is one of  toxic heavy metal that widely used  in industry thus Cd  is highly  persistent in the environment, it effects on human health by occupational and environmental exposure. Cd exerts  multiple  toxic  effects  and  has  been  classified  as  a  human  carcinogen  by  the  International  Agency  for  Research  on  Cancer  (IARC).  Cd is carcinogenesis that causes some cytotoxic effect by  disruption   gene  expression, inhibition of DNA repair systems , induction oxidative stress, and  inhibition of apoptosis (Joseph,2009) Cobalt  (Co) is an essential trace element being an integral part of vitamin B12 which is essential for folate and fatty acid metabolism. The carcinogenic potential of cobalt and its compounds was evaluated by IARC in 1991,which concluded that there was inadequate evidence for carcinogenicity in humans (lung cancer) (IARC , 1991)  . There are two different mechanisms of cobalt genotoxicity, DNA breakage induced by cobalt metal , especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions which contribute to the carcinogenic potential of cobalt compounds the experimental systems show index that soluble cobalt (II) cations extend a genotoxic and carcinogenic activity in vitro and in vivo in but lacking in humans. Experimental data mention some arguments of cobalt metals genotoxic potential in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. The genotoxic and carcinogenic activity of cobalt particals in vitro and in human studies was be recorded but  insufficient information for cobalt oxides and other compounds (Lison et al., 2013). Zinc (Zn) is a trace mineral which is important for the functioning of some cellular  activities , is contribute  in growth, and play an important role  in cancer causes and outcome , The levels of this mineral in cells are regulated by coordinated expression of zinc transporters proteins , which modulate both zinc influx as well as efflux. LIV-1 ZIP6 proteins was first described in 1988 as an estrogen regulated gene with later work suggesting  a role for this transporter in cancer developments  and metastasis(Grattan and Freake, 2012). Manganese (Mn) is one of the essential elements in living organisms and is naturally present environment . high level uptake of Mn by mouth or parenteral, or ambient air concentrations can causes increased Mn in tissue and neurological effects. However, current understanding of the impact of Mn exposure on the nervous system leads to the no adverse effects at low exposures, although Mn is an essential element in body but it mustn’t  be cross  some threshold of its  exposure because adverse effects can occur and increase in frequency with higher dose . little study found that Mn neurotoxicity include what the clinical significance is of the neurobehavioural, neuropsychological, or neurological endpoints tested in many of the occupational studies that have detected groups  exposed to low levels of Mn (Santamaria,2008). Mn toxicity has observed in occupational settings where there is the potential for chronic exposure to Journal of Pharmacy and Alternative Medicine                                                                                                                                 www.iiste.org ISSN 2222-4807 (online) ISSN 2222-5668 (Paper) An International Peer-reviewed Journal Vol.6, 2015  35 high levels or following the accidental ingestion of large quantities (Bolte et al 2004).   Materials and methods  Cancer tissue sample was obtained from AL-Hasanian  histopathe  Lab which is detected by Dr. liwaa Hussein al-kilabi , 40 samples was used in this study 20 samples were cancer while the other 20 sample were benign, sample was whashing using DH2O more than one time then e heavy metals determined in soft tissue as fallowing according to (Otchere, 2003). 1- Pulled out the soft tissue from samples by plastic forceps and put in polyethylene dishes with removing the excessive water by filter paper. 2- Tissue dried on 70 C˚ for 24 hr. with well grinding by Ceramic mortar. 3- (0.3) g has been taken from dried grinded samples and put it on Teflon Beaker , then added 10 ml from.HNO3 with heating on 85 C˚ for 1hr . After that , few drops of hydrogen peroxide added for completion of oxidation process within temperature increasing up to 135 C˚  for 30 min. until we have a clear solution and left it for a while to get a cooling and complete by D.D.W up to 50 ml , and centrifuge this sample to remove suspended lipid compounds in case of presence for 10 min. at 2500 r.p.m and sample transferred to polyethylene bottle to be ready for measurement by Atomic Absorption Spectrophotometer type 6300(Shimadzu, Japan) and results expressed as µg/g. The Following equation was used to determine the concentration of heavy metals as µg/g. Conc = AxBxd.f ̸  D                                               conc. = Metal concentration in sample (µg/g dry weight) A= Metal concentration from standard curve (mg/L) B= Final volume for filterable samples (ml) Df= Dilution factor and used as follow ; Df =  Volume of dilution sample solution ml ̸ Volume of aliquot taken for dilution in ml D= dry weight (g). Results  Sample characterization in present study show that Age mean was 41.66  years, samples consist of high percentage of different cancer tissue it was 72.41% and 27.58 % was benign tissue. According to gender samples consist of 55.55% female and 44.44% male table (1).  Table (1) Characterization of tumor samples used in present study. Character of sample  Percentage  Age  41.66±22.68 Benign  27.58% Cancer  72.41% Female    55.55% Mal  44.44%   In cancer tissue trace elements concentrations were higher than its concentrations in benign tissue, these elements were Co and Zn, while others elements were lower in cancer tissue, all variation was non-significant, table (2).  Table (2) Trace elements concentrations in human tumor tissue in µg\g. Trace elements  Mn Cd Co Zn  Cancer tissue  1999.87±421.18 114.54±0.05 156.7±6.50 205.79±19.75 Benign tissue   2110.73±557.00 114.57±0.065 153.59±6.33 196.89±22.34 mean±SD    According to gender, in cancer tissue females had higher concentration of Mn, CO and Zn, same results was showed in benign tissue; Mn, Co and Zn concentration were higher than male table (3). Table (3) Trace elements concentration Ppm in human according to gender µg\g  Trace elements  Mn cd co Zn  Cancer tissue  Male  1998.14±413.59 114.54±0.05 156.44±6.71 204.9±18.98 Female  2011.41±439.79 114..54±0.05 157.05±6.50 206.58±20.93 Benign tissue   Male  1848.1±212.08 114.57±0.073 152.68±9.093 189.14±14.40 Female  2373.37±703.56 114.56±0.06 154.50±29.4 204.65±28.23 mean±SD  Discussion  The Genotoxic effects of metals can be mediated either through metabolically activated electrophilic derivatives Journal of Pharmacy and Alternative Medicine                                                                                                                                 www.iiste.org ISSN 2222-4807 (online) ISSN 2222-5668 (Paper) An International Peer-reviewed Journal Vol.6, 2015  36 that interact with DNA and other macromolecules, or through direct  binding of DNA (De Bont and van Larebeke 2004).  Many metals have been shown to directly  modify and/or damage DNA by forming DNA adducts that induce chromosomal breaks (Chakrabarti 2001). Susceptibility to cancer is characterized by extensive DNA damage. This damage is thought to result from decreased repair capacity and/or by the direct carcinogenic interaction of metallic ions with DNA and  DNA adducts (KLAUNIG,2010) Study show that even low doses and short term exposure to cadmium can cause specific DNA damage in breast tissue and may be a possible mechanism of action of cadmium on the cell cycle of human mammary cell lines (Roy et al. 2004).  Cadmium significantly stimulated the growth of MCF-7 cells when compared with cells grown in estrogen-depleted medium, comparable with the degree of growth stimulated by estradiol (Roy et al., 2004). This study demonstrates that cadmium induces cell growth, and may have a possible role  Since zinc is essential for growth and cancer is characterized by uncontrolled growth ,zinc accumulation suggests an involvement of zinc in breast tumor genesis. Zinc is important to cell proliferation; however, it accumulates in mammary tumors and supports tumor growth (Sukumar et al. 1983; Lee et al. 2003).   In one study twenty-one-day old female rats were assigned to a low-zinc, an adequate-zinc, or ad libitum control groups.  On day 50, all rats were injected with 1-methyl-1-nitrosourea (MNU) to induce mammary tumors. MNU has been widely used in rodent models to induce diverse mammary tumors that differ in type and location of formation in the mammary gland for studying human breast cancer due to their similarities in hormone dependency. The carcinogenicity of MNU is due to its ability to induce a mutation in the H-ras oncogene (Lee et al. 2004).  Results indicated low-zinc intake suppressed MNU-induced tumor incidence, tumor numbers and tumor multiplicity. In Iraqi environment many studies improved increasing heavy metals in human body, in study on lactating mothers milk Ziadan et al (no published data ) found that increasing in Mn, Co, Zn and Cd in mothers milk in Hilla city also Al-muhanna (2011) found increasing in heavy metals Pb , Fe and Ni. In environment researchers found that Iraqi river air and soil was polluted by different heavy metals (Salman et al .,2007; Hassan et al ., 2009) this led us to concluded that increasing heavy metals in human especially in tumors tissue resulted from environment that may be responsible on carcinogenesis and cusses cancer.   References        1. IARC (1993) Monographs on the Evaluation of Carcinogenic Risks to Humans. IARC, Lyon 119-237   2- Joseph  P  (2009)  Mechanisms  of  cadmium  carcinogenesis.  Toxicol  Appl  Pharmacol  238:272-9 .doi:10.1016/j.taap.2009.01.011   3- Taha N. D. ,Hashem K. A. and Abd-alameer S. I. (2005). Determination lead in Hilla city air . First Environmental research conference .Babylon University 4- Salman J.M. , Hassan M.F. and Saleh M. M. (2007). Concentrations of nine heavy metals in muscles of fish Barbus lutes heckel , Aspiusvorax heckel, Barbus grybus heckel and hypophthalmicthyes molotrix Richardson collected from Euphrates river. J. of Environmental , 1, 5-19. 5- Hassan, M. F. , Saleh M. M. and Salman J. M. (2010). A study of physicochemical parameters and nine heavy metals in the Euphrates river, Iraq , E-J. of Chemistry 7, 685-692. 6- Otchere, F.A. (2003). Heavy metals concentrations and burden in the bivalves (Anadara (Senilia) senilis, Crassostrea tulipa & Perna perna) from lagoons in Ghana: Model to describe mechanism of accumulation and excretion. African Journal of Biotechnology, 2 (9): 280-287. 7- IARC (1991).Cobalt and cobalt compounds. IARC Monogr Eval Carcinog Risks Hum 1991;52:363–472. 8- Lison D. ; De Boeck M., Verougstraete V, Kirsch-Volders, M.(2013). Update on the genotoxicity and carcinogenicity of cobalt compounds. Occup Environ Med 2001;58:619–625. 9- Chakrabarti SK, Bai C, Subramanian KS. 2001. DNA-protein cross links   induced by nickel   compounds in isolated rat lymphocytes, role of reactive oxygen species and specific   amino acids. Toxicol Appl Pharmacol. 170:153–165. 10- Roy S.S, Mukherjee S, Mukhopadhyay S, Das SK. (2004). Differential effect of cadmium on  cholinephosphotransferase activity in normal and cancerous human mammary epithelial cell lines. Mol Cancer Ther 3(2):199-204.  11-  De Bont R, van Larebeke N. (2004). Endogenous DNA damage in humans: a review of   quantitative data. Mutagenesis 19(3):169-85. 12- Grattan B, and Freake, C.( 2012). Zinc and Cancer: Implications for LIV-1 in Breast Cancer, Nutrients, 4, 648-675. 13- Couper J. (1837)On the effects of black oxide of manganese when inhaled into the lungs. Br Ann Med Pharm 1837; 1 : 41-2. 14- Santamaria, A.(2008). Manganese exposure, essentiality & toxicity, Indian J Med Res 128, October 2008, 484-500. Journal of Pharmacy and Alternative Medicine                                                                                                                                 www.iiste.org ISSN 2222-4807 (online) ISSN 2222-5668 (Paper) An International Peer-reviewed Journal Vol.6, 2015  37 15- Lee,R., Woo,W., Wu,W.B., Kummer,A., Duminy,H. and Xu,Z. (2003) Zinc   accumulation in N-  methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered   expression of ZnT-1 and metallothionein. Exp Biol Med 228:689-696. 16- Bolte S, Normandin L, Kennedy G, Zayed J. Human exposure to respirable manganese in outdoor and indoor air in urban and rural areas. J Toxicol Environ Health A 2004; 67 : 459-67.  17- Lee S, Simpson M, Nimmo M and Xu Z.( 2004). Low zinc intake suppressed N-methyl-N-  nitrosourea-induced mammary tumorigenesis in Sprague-  Dawley rats. Carcinogenesis 25(10):1879-1885. 18- KLAUNIG J. , KAMENDULIS M. , AND HOCEVAR B. (2010). Oxidative Stress and Oxidative Damage in Carcinogenesis,  Toxicologic Pathology, 38: 96-109. 19- Sukumar S, Notario V, Martin-Zanca D, Barbacid M. 1983 Induction of mammary carcinomas in rats by nitroso-methylurea involves malignant activation of H-ras-1 locus by single point  mutations. Nature 306(5944):658-61. 20- Al-Muhana, E. (2012) DETERMINATION OF SOME HEAVEY METALS (LEAD, CADIMUM, NICKEL AND IRON) IN BREST MILK OF LACTATING MOTHERS IN HILLA CITY-2012. Diploma thesis college of medicine.           The IISTE is a pioneer in the Open-Access hosting service and academic event management.  The aim of the firm is Accelerating Global Knowledge Sharing.  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Heavy Metals Concentration Detection in Tumor Tissue

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Heavy Metals Concentration Detection in Tumor Tissue

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