10. Metabolic activation of mutagens PROMUTAGEN ACTIVE (ULTIMATE) MUTAGEN DNA ADDUCT (OR OTHER CHEMICAL MODIFICATION OF DNA BASES) MUTATION enzymes metabolic activation TUMOR liver
22. Ames test His – bacteria Dies in a normal medium Medium containing histidine Normal medium His + bacteria Reverse mutation Mutagen
23. Ames test 0 Negative control Positive control A dish with a compound to be tested GENOTOXICITY CONFIRMED S PONTANEOUS REVERTANTS IS USED FOR CONTROL OF THE TEST COMPOUND CONFIRME D MUTAGENIC COMPOUND
27. Result of the task Number of colonies decreases due to toxic effects of the tested compound Number of revertant colonies Dose of 1-nitropyrene (micrograms per dish) Number of colonies increases with the dose – mutagenicity confirmed.
31. Possible results of chromosomal analysis Mutagenic effect confirmed with high probability More than 4% A border result – mutagenic effect is neither confirmed nor excluded 2 – 4 % Normal finding, spontaneous level of aberrations Less then 2% Result Percentage of cells with chromosomal aberrations
32.
33. Sister Chromatid Exchanges Normal chromosome A chromosome with SCE The higher SCE frequency – the higher mutagenic activity.
35. Carcinogenesis (simplified scheme) mutagen mutagen apoptosis mutation repaired A cell with the first mutation A cell with the second mutation Dividing tumor cells normal cell normal cell „ Rubicon“
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39. IARC database International Agency for Research of Cancer
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