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