There are many different cell lines that have been used in order to examine genotoxicity exposure of agents such as human gastric adenocarcinoma cell line - TMK1, human colon cancer - COL2, particularly human B lymphoblastoid cell line - TK6 is more often used. TK6 is a cell line heterozygous at the thymidine kinase locus from a patient with chronic myelogenous leukemia (CML) in T cell lineage blast crisis which included Philadelphia chromosome t(9;22)(q34;q11), an abnormality in chromosome 6 (a deletion of the long arm), and chromosome 7, for example, del(6)(q21); ins(1;-)(q21;-); del(1)(q21;q32); dic(7)(:p13 cen q32:11.2 cen pter) (Watanabe et al., 1995; Tomita et al., 1998). These cells are relatively stable p53-normal immortal, have low mutation frequencies in gene and chromosome, and are proficient in mismatch repair (Tomita-Mitchel et al., 2000), from these properties TK6 cell line is applied in this study for assessing toxicity of anti-cancer agents.
Polyynes containing triple bonds which are presented in many natural sources, have been considered in medicine with a variety of biological activities such as antifungal, anti-inflammatory, antibacterial, antimicrobial, antiHIV, and anticancer (Dembitsky et al., 2006). Previously, there were many researches about the diyne-structure-related-capability of polyyne, especially ene-diyne, these investigations suggested that enediyne compounds include two triple bonds (diyne) seperated by a double bond (ene) can cleavage DNA via cross linking to several positions, interacting with minor groove or abstracting hydrogen atoms as well as arrest cell cycle, inhibit proteins required for initiation replication stage (Chin et al., 1988; Sugiura et al., 1989; Walker et a...
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... nuclei, and should be separated with clear nuclear boundary.
Along with the proposal, the RAGS system will be completed and approved in week 18. After that, the first step is synthesis of two chemicals in 4 weeks from 16th January to 13th February 2012. Once the chemicals are produced, TK6 cells will be treated in control medium and in medium containing these compounds, separately, and measure LD50¬ of TK6 cell line, statistic analysis LOEC, NOEC and thereby comparing cytotoxicity of these compounds. This process will take around 6 weeks from 13th February to 23rd March 2012. Later on, micronucleus assay will be applied to study genotoxicity on TK6 cells via clastogenic behaviour for 7 weeks and finish laboratory practical on 1st June 2012. Finally, writing up and project draft will be completed within 4 weeks.
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