karsinogen dan karsinogenesis
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KARSINOGEN DAN
KARSINOGENESISDr Aswiyanti Asri,M.Si.Med,SpPA
Karakteristik sel kanker
Diferensiasi <<, tidak relevan dengan fungsi tubuh (normal).
Inti abnormal (membesar), dan mungkin jumlah kromosom.
Kemampuan membelah tidak terbatas : telomerase.
Membentuk massa tumor. Dapat membelah diri tanpa growth
factors. Abnormalitas terbentuk melalaui proses
multistage. Mengalami angiogenesis dan metastasis.
Environmental vs. Hereditary Cancer85
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Cancer Etiology
Environmental Hereditary
Agen (lingkungan) penyebab kanker
3 kelompok utama :•Kimiawi•Fisika (radiasi)•Biologi (terutama virus)
Aflatoxins Asbestos Benzene Cadmium Coal tar
Creosote DDT Polycyclic
aromatic hydrocarbons
Radon Solar
radiation
Adriamycin (doxorubicin)
Androgenic steroids
Chlorambucil Cisplatin Cyclophosphamide Cyclosporin A
Diethylstilbestrol
Ethylene oxide
Melphalan Tamoxifen
Direct-acting : electrophilic•Nitrogen mustard•Nitrosomethylurea•Benzyl chloride
Indirect-acting (dimetabolisme menjadi bentuk aktif : Polycyclic aromatic hydrocarbons (PAH)•Terbentuk dari pembakaran tidak sempurna material organik
•Cerobong asap, makanan yang dibakar, rokok.
Electrophilic (electron-seeking) molecules will bind to nucleophilic (electron-rich) macromolecules in the cell• DNA• RNA• Proteins
Ultraviolet light Ionizing radiation (X-rays)
Asbestos
Direct effect on DNAActivation of cellular oncogenes
UV light is believed to induce cross-linkages between DNA molecules and Cancer occurs when repair mechanisms are not efficient
1 dari 7 kanker disebabkan virus, t.u virus DNA
Human papillomaviruses - HPV Epstein-Barr Virus (EBV) Human herpes virus 8 (HHV8) Hepatitis B virus - HBV Hepatitis C virus - HCV HTLV-I, HTLV-II
Very small viruses Can integrate their viral DNA into
host genome They code for viral proteins which
block tumor suppressor proteins in cells
Gastric infection linked to gastric lymphomas and adenocarcinomas
Detection of H pylori in majority of cases of gastric lymphomas
Antibiotic treatment results in gastric lymphoma regression in most cases
Multistage theory of carcinogenesis
What is epigenetic ?•Epigenetic refers to all heritable changes in gene expression and chromatin organization that occur without alteration in DNA sequence.•Epigenetic changes do not depend on DNA sequence changes. They do depend on modification of the DNA, but on modifications that leave the basic sequences of A, G, C and T nucleotides unchanged..•Level transkripsi, translasi dan posttranslasi
Epigenetics Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetics stands at the center of modern medicine because epigenetic changes, unlike DNA sequence which is the same in every cell, can occur as a result of dietary and other environmental exposure
DNA Methylation and Cancer
Robertson, Nature Reviews Genetics, Vol6, 597
Histone Modifications
http://porpax.bio.miami.edu/~cmallery/150/gene/c7.19.4.histone.mod.jpg
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