Apoptosis dan Respon Biologik Sel sebagai Faktor Prognosa Radioterapi Kanker

Kanker merupakan masalah paling utama dalam bidang kedokteran dan merupakan salah satu dari 10 penyebab kematian utama di dunia serta merupakan penyakit keganasan yang bisa mengakibatkan kematian pada penderitanya karena sel kanker merusak sel lain. Sel kanker adalah sel normal yang mengalami mutasi/Perubahan genetik dan tumbuh tanpa terkoordinasi dengan sel-sel tubuh lain. Proses pembentukan kanker (karsinogenesis) merupakan kejadian somatik dan sejak lama diduga disebabkan karena akumulasi Perubahan genetik dan epigenetik yang menyebabkan Perubahan dalam pengaturan normal kontrol molekuler perkembang biakan sel. Perubahan genetik tersebut dapat berupa aktivasi proto-onkogen dan atau inaktivasi gen penekan tumor yang dapat memicu pembentukan tumor. Berbagai macam percobaan (bahkan sampai jutaan) telah dilakukan untuk mempelajari karakteristika suatu kanker dengan menggunakan hewan percobaan seperti tikus, mencit, anjing, domba, bahkan organisme bersel tunggal, dll [1]

Dosimetri Biologik Sitogenetik Pada Liquidator Kecelakaan Chernobyl

CYTOGENETIC BIOLOGICAL DOSIMETRY IN THE LIQUIDATORS OF CHERNOBYLACCIDENT. When human body exposes to ionizing radiation, the most important kind of damage are double strand breaks of DNA. Misrepair of the damages can lead to morphological changes inchromosomes known as chromosomal aberrations. Measurement of chromosome aberrations inblood peripheral lymphocyte cells has been applied to assess dose received by potentiallyoverexposed people and estimate risk for health effects in radiation or nuclear accident cases.Dicentric and translocation are the most important types of chromosome aberrations in biologicaldosimetry or biodosimetry which is usually used when there is no physical dosimetry available or when irradiation dose needs to be confirmed.The cytogenetic screening had been carried out inChernobyl accident for biological doses estimated from dicentric and translocation yields inliquidators (clean-up workers). This paper reviews the cytogenetical biodosimetry application inChernobyl accident liquidators that has proved the worth of the method. Absorbed dose estimatesderived using cytogenetic data and dose response calibration curves are based on the assumption that all individuals have equally respond to radiation

Micronucleus Frequencies and DNA Repair Gene XRCC3 Polymorphism in Radiation Workers of Center for Multipurpose Reactor

The carcinogenic effects of low radiation doses have not been fully understood until now. Studies on individuals that are occupationally exposed to low radiation doses can help to address this question. This study assesses the micronucleus (MN) frequencies as indicator of DNA damage in radiation workers that are occupationally exposed to low radiation dose. The influence of single nucleotide polymorphisms (SNPs) in XRCC3 gene on the frequency of micronuclei was also evaluated in this study. The effects of confounding factors of gender, age, and smoking status on MN frequencies was assessed in all samples. A total of 60 subjects consisting of 30 radiation workers from Center of Multipurpose Reactor (CMPR), National Nuclear Energy Agency (NNEA) of Indonesia, and 30 control samples were enrolled in this study. The results showed that the difference between MN frequency in radiation workers and in control samples was not statistically significant [0.019 vs. 0.021; p = 0.549]. Age and smoking status did not affect micronucleus frequencies in all samples (p = 0.723 and 0.828). Micronucleus frequencies in females were higher compared to males, even though the difference was not significant (p = 0.3). Radiation workers with variant alleles for XRCC3 olymorphism did not showed higher MN frequencies compared to the controls with the same genotypes. The small numbers of samples with XRCC3 variant alleles found in this study possibly contributed to the insignificant difference of MN frequencies between wild-type allele (Thr/Thr) and mutant alleles (Thr/Met or Met/Met). Further investigations using larger sample sizes and MN assay in combination with human pan-centromeric probe should be conducted to validate this study results. Other SNP in XRCC3 gene also should be evaluated to find out the association between SNP and MN frequencies

Otomatisasi Pendeteksian Sel Blast dan Sel Metafase dengan Perangkat Lunak Pengolahan Citra Sumber Terbuka

Tingkat toksisitas suatu senyawa dapat diketahui berdasarkan nilai indeks mitosis pada sel limfosit darah tepi. Analisis indeks mitosis pada umumnya dilakukan secara manual menggunakan mikroskop cahaya pada perbesaran rendah dengan mengidentifikasi sel metafase dan sel blast (nukleus sel interfase yang terstimulasi). Proses identifikasi sel blast dan sel metafase dapat dilakukan secara otomatis menggunakan perangkat lunak pengolahan citra sumber terbuka yaitu ImageJ 1.47. Program macro yang dapat mendeteksi secara otomatis blast dan sel metafase telah dibuat untuk memudahkan analisis indeks mitosis. Tujuan penelitian ini adalah mengetahui keakuratan program macro pada ImageJ 1.47 untuk mendeteksi secara otomatis sel blast dan sel metafase. Sampel darah tepi dari tiga donor berbeda dibiakkan dan dibuat preparatnya, kemudian sebanyak tiga puluh citra dari setiap donor dianalisis menggunakan program macro yang dibuat. Hasil penghitungan jumlah total sel blast dan sel metafase secara otomatis dan manual diolah secara statistik menggunakan Uji T. Taraf nyata yang digunakan (α) adalah 0,05. Hasil penelitian menunjukkan bahwa tidak terdapat perbedaan nyata antara jumlah sel blast dan sel metafase yang diperoleh secara otomatis dengan manual (P = 0,69 dan P = 0). Jumlah sel blast dan sel metafase yang dihitung secara otomatis lebih rendah (underestimated) dibandingkan nilai sebenarnya. Beberapa faktor yang menyebabkan hal tersebut akan dibahas secara terperinci didalam makalah. Secara keseluruhan program macro yang dibuat dapat digunakan untuk mendeteksi dan menghitung dengan jumlah total sel blast dan sel metafase, meskipun hasil yang diperoleh tidak lebih baik dari hasil penghitungan secara manual. Pengembangan lebih lanjut terhadap program macro atau penggunaan perangkat lunak pengolahan citra yang dikhususkan untuk bidang biologi yaitu CellProfiler 2.0 perlu dilakukan sehingga penghitungan nilai indeks mitosis dapat dilakukan secara lebih cepat dan akurat untuk mengetahui tingkat toksisitas suatu senyawa

Assessment of Ionizing Radiation Induced Dicentric Chromosome and Micronuclei in Human Peripheral Blood Lymphocytes for Preliminary Reconstruction of Cytogenetic Biodosimetry

Cytological biodosimetry methodology has been widely used for determining and estimating the precise irradiation dose received by victims in the situation of emergency irradiation exposure. The aim of this study was to assess the gamma-ray induced dicentric chromosomes and micronuclei (MN) in peripheral blood lymphocytes for preliminary reconstruction of cytogenetic biodosimetry. The study was performed by exposing blood samples taken from seven healthy donors to gamma rays at dose range of 0.1 to 4.0 Gy, followed by culturing them for 48-72 hours at 37 °C by the standard technique. After being harvested, the chromosome spread at metaphase and MN were stained with Giemsa's solution. The results showed that the frequency of both dicentrics and MN of samples were increased with the increase of radiation dose. Considerable increases of both cytologic damages were found in the samples exposed to higher doses (>2 Gy). Significant differences (p>0.05) only found in mean frequencies of MN for all doses tested. Reconstruction of the relationship of these frequencies with doses was found to follow linear-quadratic curve lines and was consistent with that of other studies. Due to the aforementioned advantages namely the dependence of radiation dose and dose rate on the frequency of of both dicentric and MN, despite some limitations, these assays have been found to be suitable to be used as biological dosimetry.  It is concluded that in order for this cytogenetic biodosimety method by means of scoring/assessing the radiation-induced dicentrics and MN could be used in radiation emergency and protection, and further studies with larger numbers of samples need to be done.Received: 12 November 2015; Revised: 18 Mei 2016; Accepted: 08 December 201

Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation.In radiation accident the dicentric assays has been applied as biological dosimetry to estimate  radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric) in human lymphocyte inducedbygamma radiation. Peripheral blood samplesfrom three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018± 0.006 and 0.013 ± 0.002,respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validatedReceived: 8 November 2013; Revised: 27 December 2013; Accepted: 31 December 201

Polymorphism of XRCC1 Gene Exon 6 (Arg194Trp) in Relation to Micronucleus Frequencies in Hospital Radiation Workers

The genetic polymorphism of DNA repair gene plays some important role in regulating individual sensitivity to ionizing radiation, maintaining DNA integrity, and preventing cancer and DNA damage.XRCC1 as one of the members ofbase excision repair (BER) is involved in the repairement of oxidized bases and single-strand breaks DNA after exposure by ROS, including ionizing radiation. This study was aimed to examine the correlation between XRCC1 exon 6 gene polymorphism and MN frequency in radiation workers and their relation to age, gender, smoking status and years of exposure. This study involved 81 hospital radiation workers and 20 controls from several hospitals in Indonesia. Genotyping of XRCC1exon 6 gene polymorphism and MN assay were performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Cytokinesis-Block Micronucleus assay (CBMN assay), respectively.  The results indicated that MN frequency was significantly higherin the exposed workers than in the controls (15.38±7.72 versus 9±5.49; p = 0.001).Radiation workers with heterozygous alleles for XRCC1 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes (17.5±8.36 versus 7.44±5.05; p = 0.002). The confounding factors, like gender and age, were significantly associated with increased MN frequency both in radiation workers and controls. Smoking status was significantly associated with MN frequency in the controls only, while years of exposure did not affect MN frequency either in radiation workers or controls. These results suggest that the genetic polymorphism of XRCC1 gene exon 6 with a mutant heterozygous/ CT variant demonstrated an association with the extent of DNA damage in the hospital radiation workers in this study. In the subsequent studies, it is necessary to examine the DNA repair genes polymorphism in populations with controlled non-genetic factors, such as lifestyles, environments, and exercises that affect the MN frequency as a biomarker of DNA damage

PEMODELAN WAKTU TUNGGU PENUMPANG PADA JALUR ANGKUTAN DALAM KOTA PALU MENGGUNAKAN ALJABAR MAX-PLUS

Passenger waiting time is the time required by passengers starting from the stops until getting transport. The purpose of this research is to get the model of waiting time passengers on the freight line in the Palu city. The first step is the preparation of directed graphs based on the existring routes, then calculate the mileage and travel time using synchronization rules and power algorithm with initial vector = 0 obtained the value = 2, = 1 and = 102by using the appplication rock Scilab 5.5.2 and Map-Plus Toolbox obtained eigenvalues as the departure period of 102 and eigenvektor as the initial departure time.Keywords : Eigenvalues, Eigenvectors, Max-Plus Algebra, Waiting Time