KARSINOGEN DAN KARSINOGENESIS

Presentasi berjudul: "KARSINOGEN DAN KARSINOGENESIS"— Transcript presentasi:

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

2 Karsinogen vs Karsinogenesis
Kanker

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4 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.

5 Six hallmarks of cancer

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7 Environmental vs. Hereditary Cancer

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

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

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

13 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.

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

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

17 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

18 Viral carcinogenesis 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

19 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

20 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

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28 Multistage theory of carcinogenesis
Inisiasi Promosi Progresi

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38 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

39 Epigenetics Mechanisms
RNA Interference Gene Expression DNA Methylation Histone Modifications

40 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

41 DNA Methylation and Cancer
Robertson, Nature Reviews Genetics, Vol6, 597

42 Histone Modifications

43 Epigenetic changes

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47 THANK YOU