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Dr. Djoko Agus Purwanto, Apt., M.Si.

PENGARUH MAKANAN TERHADAP KANKER. Dr. Djoko Agus Purwanto, Apt., M.Si. Penyebab Kanker. Radiasi gel. elektromagnetik Virus Senyawa Kimia (Karsinogen). Cancer. Cancer is the uncontrolled growth of cells due to damage to DNA (mutations)

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Dr. Djoko Agus Purwanto, Apt., M.Si.

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  1. PENGARUH MAKANAN TERHADAP KANKER Dr. Djoko Agus Purwanto, Apt., M.Si.

  2. Penyebab Kanker • Radiasi gel. elektromagnetik • Virus • Senyawa Kimia (Karsinogen)

  3. Cancer • Cancer is the uncontrolled growth of cells due to damage to DNA (mutations) • In adult life, normal cells grow and divide to form new cells only when the body needs them (to replace worn-out or dying cells and to repair injuries) • Mutations can sometimes disrupt this orderly process. New cells form when the body does not need them, and old cells do not die when they should • These extra cells produce a tumour that may be cancerous

  4. Tahapan terjadinya kanker INISIASI Sel masih memiliki fenotip normal PROMOSI Sel premalignan PROMOSI Ekspnasi klon sel premalignan PROGRESI Sel malignan Ekspnasi klon sel malignan METASTASES

  5. SEL KANKER

  6. Tumour cells are visible to the immune systemThe immune system exists to recognise and respond to non-selfMany studies prove beyond doubt:CANCER IS IMMUNOGENIC.........and tumour-specific T cells can destroy tumours and cure mice

  7. Hypothesis The innate immune system first recognises tumour cells and produces IFN- Inflammatory cascade causes limited tumour cell death and dendritic cells then transport tumour products to the draining lymph node (Dunn et al., Nature Immunol Nov. 2002)

  8. The natural immune system controls tumour while specific T cells develop in the lymph nodes Specific T cells (mostly CD8) infiltrate the tumour and destroy cells expressing appropriate tumour antigens

  9. A cancer cell under attack by T cells of the immune system Cancer cell killed

  10. Tumour escape is the main hurdle • for immunotherapy • Tumours predominantly employ two escape strategies: • Antigen loss • Immunosuppression

  11. Antigen loss (Khong & Restifo, Nature Immunol Nov 2002)

  12. Immunosuppression • The tumour environment is immunosuppressive • Production of soluble factors (IL 10, TGF-ß) • Destruction of tumour-infiltrating cells (fas; free radicals) • Defusing tumour-infiltrating cells (anergy induction) • Induction of suppressor cells (Treg) • Clonal exhaustion (proliferative senescence)

  13. Radiasi Gelombang Elektromagnetik • Sinar UV • Sinar X • Sinar Gama • Sinar Kosmis • radiasi senyawa radioaktif misalnya dari gas radon

  14. VIRUS • Rous Sarcoma (ayam) • Simian Sarcoma virus (monyet) • Avian erythroblastosis (ayam) • Hepatitis B virus, • Feline sarcoma (kucing)

  15. Senyawa Kimia • Glu-P1, Glu-P2  hasil pembakaran glutamat • Trp-1, Trp-2 hasil pembakaran triptopan • Rodamin B  zat warna (sumba) • Nitrosamin  dalam lemak hewan  babi • Nitrit/nitrat  pengawet ikan/daging • Benzopyren  pada rokok

  16. Many carcinogens in our food or environment around us • Cigarette smoke Benzo(a)pyrene • Pyrolisis of amino acid Glu-P1, Glu-P2, Trp-1, Trp-2 • Aspergillus flavus Aflatoxin B1 • (in peanut/groundnut meal) • Animal fats Nitrosamine • Nitrate/nitrite in food Nitrosamine • Potatoes crisps, biscuit Acrylamid • Asbestos particles (from environment) • Polycyclic aromatic hydrocarbon • Pesticide Carbamyl, Diazinon • Aerosol product, spray Methylen chloride • Etc.

  17. Jamur Aspergilus flavus pada jagung menyebabkan terjadinya kanker hati

  18. Conidial head of Aspergilus flavus

  19. The risk of colorectal cancer according to dietary fat intake Whittemore AS, Wu-Willaims AH. Lee. JNC 1990;82:915.

  20. Alkylation induces specific mispairing The alkylation of the O-6 position of guanine can lead to direct mispairing with thymine and the O-4 position of thymine can lead mispairing with guanine.

  21. Methylation of O6-position of guanine O6-position Alkilasi adalah penambahan gugus metil atau etil pada Basa DNA. Pada contoh disini adalah alkilasi pada posisi O6-guanine membentuk O6-methylguanine.

  22. Repair of O6-methylguanine by AGT(Alkylguanine-DNA Alkyltransferase) methyl- AGT AGT-methyl (inactive) AGT transfers the methyl group from O6-methylguanine to a cysteine residue in the enzyme's active site.

  23. AGT will be inactive after remove the alkyl from DNA(suicide reaction) High level of alkylation The repair system can be saturated can not make repair again Mutation

  24. Contoh karsinogen AGT AMAN 60 molekul 100 molekul BORDERLINE (WARNING) 100 molekul 100 molekul DANGEROUS 120 molekul 100 molekul 20 molekul tidak dapat diperbaiki !!!

  25. What genes that had important role in carcinogenesis? • At least, there two group of genes: • Proto-oncogens • Tumor-suppressor genes

  26. Proto-oncogen K-ras normally mutated Lost of GTPase activity GTPase activity (GTP  GDP) continuously ploriferation regulates the cellular ploriferation Cancer

  27. Dapatkah EGCG dari teh hijau dapat mencegah kanker?? • EGCG 25 kali lebih poten dari Vit.E • EGCG 100 kali lebih poten dari Vit. C • EGCG 2 kali lebih poten dari Resveratrol yang terdapat pada red wine

  28. Pengaruh pemberian inisiator (I) dan promotor (P) terhadap pembentukan tumor I Tidak terjadi tumor I PPPPPPPPP Terjadi tumor PPPPPPPPP Tidak terjadi tumor PPPPPPPPPI Tidak terjadi tumor I PPPPPPPP Terjadi tumor I P P P P P P P Tidak terjadi tumor Waktu

  29. Hal yang Perlu dalam Pencegahan Kanker • Hindari rokok yang telah terbukti dapat memicu terjadinya kanker dan juga makanan-makanan yang dicurigai dapat menimbulkan kanker seperti beberapa pewarna kain yang telah dilarang penggunaannya untuk pewarna makanan. • Makanan berlemak banyak mengandung nitrosamin yang dapat menyebabkan kanker. • Daging yang dibakar menyebabkan terbentuknya bahan karsinogen, oleh karena itu sedapat mungkin dikurangi sebagai makanan kegemaran. • Hati-hati dengan kacang-kacangan yang telah ditumbuhi jamur. Boleh jadi jamur tersebut adalah Aspergillus flavus yang dapat menghasilkan aflatoksin B1yang dapat menyebabkan kanker hati.

  30. Hal yang Perlu dalam Pencegahan Kanker (Lanjutan) Hindari berbagai macam radiasi kecuali memang sangat diperlukan seperti sinar Rontgen.Hindari virus yang berasal dari hewan ternak/piaraan misalnya ayam, burung, kucing, anjing dan sebagainya.Makanlah makanan yang bergizi dan mengandung antioksidan seperti buah-buahan segar, wortel, makanan yang mengandung vitamin C, vitamin E serta teh hijau.Pastikan bahwa makanan kegemaran merupakan makanan yang sehat dari jauh dari kecurigaan dapat menyebabkan kanker karena tentu makanan ini sering diulang dalam waktu dekat. Untuk menghindari paparan promotor secara terus menerus.

  31. Thank you very much for your audience

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