Uji Karsinogenik & Mutagenik

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KARSINOGENESIS DAN MUTAGENESIS

MUTAGENESIS : INDUKSI THDP BERBAGAI PERUBAHAN KADAR INFORMASI DR SUATU ORGANISME/SEL YG TDK DISEBABKAN PROSES REKOMBINAN NORMAL

4 KATEGORI UTAMA UJI MUTAGENESIS


1. MUTASI

GEN 2. PERUBAHAN KROMOSOM 3. PERBAIKAN DNA DAN REKOMBINASI 4. UJI LAIN EVALUASI PEMILIHAN SIST UJI DILAKUKAN BILA DIDPT HASIL NEGATIF PALSU, SHG DILAKUKAN SERANGKAIAN UJI

Why the Ames test is so useful


a. it is fast: requires just a few days to complete b. can be performed easily c. many compounds can be tested at one time d. it is very sensitive: can detect one mutation per billion cells e. can detect mutagaens formed as a result of normal cellular function

Elements of Ames test


a. tryptophan requiring Salmonella typhimurium: requires tryptophan to grow tryp- bacteria b. smooth endoplasmic reticulum from mouse liver: contains liver enzymes that detoxify ingested material. These enzymes can produce mutagens from normally nonmutagenic chemicals that are ingested. c. chemical in question

Results of Ames test


if chemical is a mutagen then trypbacteria will be mutated to tryp+ bacteria

Doing the Ames test

KARSINOGENESITAS
KARSINOGENESIS KIMIA: INDUKSI/PENINGKATAN NEOPLASIA OLEH ZAT 2X KIMIA RESPON SUATU ORGANISME THDP KARSINOGEN: 1. ME FREKUENSI 1/BBRP JENIS TUMOR 2. PERKEMBANGAN TUMOR TDK TAMPAK DLM KLMP PEMBANDING 3. MUNCUL TUMOR LEBIH AWAL 4. JUML TUMOR LEBIH TINGG

MACAM-MACAM KARSINOGEN
LINGKUNGAN : B(a)P, ANILIN ALAM : AFLATOKSIN ELEMEN ANORGANIK: Cd, As RADIASI : X-rays

80% KARSINOGEN: ENVIRONMENTAL


COMPONENTS

KARSINOGEN BERDASARKAN CARA KERJA


KARSINOGEN

GENOTOKSIK KARSINOGEN EPIGENETIK

KARSINOGEN GENOTOKSIK

KARSINOGEN

KERJA

LANGSUNG PROKARSINOGEN

KARSINOGEN KERJA LANGSUNG


AKTIF SEC BIOLOGI BERSIFAT ELEKTROFIL LANGSUNG & SPESIFIK BERINTERAKSI DGN MAKROMOLEKUL

CTH: MUSTARD NITROGEN EPOKSID ALKIL

PROKARSINOGEN
DIAKTIVASI SEC LANGSUNG/ PEMBTKAN KARSINOGEN ANTARA Contoh: POLISIKLIK HIDROKARBON AROMATIK AFLAKTOKSIN CCL4

KARSINOGEN EPIGENETIK
KOKARSINOGEN PROMOTOR

KARSINOGEN

BENDA ASING

INISIASI
KERUSAKAN AWAL DNA YG IRREVERSIBEL
INISIASI SEL SEL NEOPLASTIK

PROMOSI
FASE II TJD PERUBAHAN DR SEL NEOPLASTIK MENJD TUMOR, YANG BERSIFAT REVERSIBEL

UJI KARSINOGENESITAS JANGKA PANJANG


HEWAN : TIKUS/MENCIT, MARMOT
SIFAT STRAIN: 1. PEKA THDP KARSINOGEN 2. INSIDEN TUMOR SPONTAN RENCAH 3. LAJU & POLA BIOTRANSFORMASI MIRIP MANUSIA

LAMA PENELTIIAN : 24 BLN TIKUS 18 BLN MENCIT CARA PEMBERIAN SAMA DGN MANUSIA DOSIS YG DIBERIKAN : HEWAN TETAP HIDUP, TAPI TUMOR AKAN MUNCUL

PENGAMATAN: BERAT BADAN&KONSUMSI PAKAN PENGAMATAN UMUM UJI LAB: HEMATOLOGI STANDAR PASCA MATI (MAKROS & MIKROSKOPIK) PELAPORAN 1. JUMLAH BERBAGAI JENIS TUMOR 2. JUMLAH HEWAN YG ADA TUMOR 3. JUMLAH TUMOR TIAP HEWAN 4. PERMULAAN MUNCUL TUMOR

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