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KARSINOGEN DAN KARSINOGENESIS

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  1. KARSINOGEN DAN KARSINOGENESIS Dr Aswiyanti Asri,M.Si.Med,SpPA

  2. Karsinogen vs Karsinogenesis

  3. 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.

  4. Six hallmarks of cancer

  5. Environmental vs. Hereditary Cancer

  6. Karsinogen lingkungan • Agen (lingkungan) penyebab kanker • 3 kelompok utama : • Kimiawi • Fisika (radiasi) • Biologi (terutama virus)

  7. Human carcinogens - environmental • Aflatoxins • Asbestos • Benzene • Cadmium • Coal tar • Creosote • DDT • Polycyclic aromatic hydrocarbons • Radon • Solar radiation

  8. Human carcinogens - drugs/therapeutic agents • Adriamycin (doxorubicin) • Androgenic steroids • Chlorambucil • Cisplatin • Cyclophosphamide • Cyclosporin A • Diethylstilbestrol • Ethylene oxide • Melphalan • Tamoxifen

  9. Karsinogen kimiawi • 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.

  10. Electrophilic Theory of Chemical Carcinogenesis • Electrophilic (electron-seeking) molecules will bind to nucleophilic (electron-rich) macromolecules in the cell • DNA • RNA • Proteins

  11. Physical Carcinogens Ultraviolet light Ionizing radiation (X-rays) Asbestos

  12. Karsinogenesis radiasi • Direct effect on DNA • Activation of cellular oncogenes • UV light is believed to induce cross-linkages between DNA molecules and Cancer occurs when repair mechanisms are not efficient

  13. Viral carcinogenesis 1 dari 7 kanker disebabkan virus, t.u virus DNA Human papillomaviruses - HPV Epstein-Barr Virus (EBV) Human herpesvirus 8 (HHV8) Hepatitis B virus - HBV Hepatitis C virus - HCV HTLV-I, HTLV-II

  14. How Do Viruses like HPV and HBV Cause Cancer? • Very small viruses • Can integrate their viral DNA into host genome • They code for viral proteins which block tumor suppressor proteins in cells

  15. Helicobacter pylori • 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

  16. Multistage theory of carcinogenesis

  17. 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 What is epigenetic ?

  18. Epigenetics Mechanisms RNA Interference Gene Expression DNA Methylation Histone Modifications

  19. 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

  20. DNA Methylation and Cancer Robertson, Nature Reviews Genetics, Vol6, 597

  21. Histone Modifications http://porpax.bio.miami.edu/~cmallery/150/gene/c7.19.4.histone.mod.jpg

  22. Epigenetic changes

  23. THANK YOU