KARSINOGEN DAN KARSINOGENESIS

Dr Aswiyanti Asri,M.Si.Med,SpPA

Karsinogen Karsinogenesis Kanker

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 Cancer

100 80 60 40 20 0

85

15

Cancer Etiology Environmental Hereditary

Agen

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

Aflatoxins Asbestos Benzene Cadmium

Creosote
DDT Polycyclic

Coal

tar

aromatic hydrocarbons Radon Solar radiation

 Adriamycin

(doxorubicin) Androgenic steroids Chlorambucil Cisplatin Cyclophosphamide Cyclosporin A

Diethylstilbestr

ol 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 (Xrays) Asbestos

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

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

Inisiasi

Promosi

Progresi

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

RNA Interference

Gene Expression

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