Cellulaire
toxicologie
,
,H1: INTRODUCTIE TOT TOXICOLOGIE ................................................................................................................................. 1
1.1 DE COMPLEXITEIT VAN TOXICOLOGIE .................................................................................................................................. 1
1.2 HET ONTSTAAN VAN TOXICOLOGIE ..................................................................................................................................... 3
1.3 DOSIS-RESPONS ............................................................................................................................................................ 5
1.4 BRONNEN EN BEWEGING VAN TOXISCHE STOFFEN .................................................................................................................. 8
1.5 ECOTOXICOLOGIE .......................................................................................................................................................... 9
1.6 TOXICITEIT ................................................................................................................................................................. 11
H2: TOXICOKINETIEK – ADME .......................................................................................................................................... 13
2.1 INTRODUCTIE TOT TOXICOKINETIEK .................................................................................................................................. 13
2.2 ABSORPTIE ................................................................................................................................................................ 14
2.3 DISTRIBUTIE ............................................................................................................................................................... 23
2.4 ELIMINATIE – EXCRETIE ................................................................................................................................................. 26
H3: TOXICOKINETIEK – BIOTRANFORMATIE ..................................................................................................................... 28
3.1 INTRODUCTIE ............................................................................................................................................................. 28
3.2 CHEMISCHE AARD VAN GIFSTOFFEN .................................................................................................................................. 29
3.3 CHEMISCHE REACTIES ................................................................................................................................................... 29
3.4 BIOTRANSFORMATIEREACTIES ......................................................................................................................................... 29
3.5 BIOTRANSFORMATIEPLAATSEN ........................................................................................................................................ 36
3.6 FACTOREN DIE BIOTRANSFORMATIE BEÏNVLOEDEN ............................................................................................................... 37
3.7 SYNERGIE, ANTAGONISME EN CHEMISCHE INTERACTIES ......................................................................................................... 37
H4: OXIDATIEVE STRESS ................................................................................................................................................... 38
4.1 INLEIDING – WAT IS OXIDATIEVE STRESS? ........................................................................................................................... 38
4.2 ONTSTAAN VAN ZUURSTOF ............................................................................................................................................ 38
4.3 GEBRUIK VAN O2 DOOR ZOOGDIEREN ............................................................................................................................... 39
4.4 WAT VEROORZAAKT DE TOXISCHE EFFECTEN VAN O2? .......................................................................................................... 40
4.5 ANTIOXIDATIEVE VERDEDIGING ....................................................................................................................................... 44
4.6 OXIDATIEVE STRESS: SCHADE VS FUNCTIE ........................................................................................................................... 47
H5: CELSCHADE ................................................................................................................................................................ 52
5.1 INLEIDING.................................................................................................................................................................. 52
5.2 CELSCHADE: RECEPTOR-GEMEDIEERDE TOXICITEIT ............................................................................................................... 54
5.3 CELSCHADE: METABOLIET-AFHANKELIJKE TOXICITEIT ............................................................................................................. 58
5.4 MECHANISMS OF ACTION: HOE METABOLIETEN CELLEN BESCHADIGEN ...................................................................................... 61
5.5 HOE ZULLEN CELLEN HIEROP REAGEREN?........................................................................................................................... 72
5.6 MECHANISTISCHE TOXICOLOGIE IN HET ‘-OMICS’ TIJDPERK..................................................................................................... 72
H6: DE CELCYCLUS ............................................................................................................................................................ 73
6.1 DE KLASSIEKE CELCYCLUS ............................................................................................................................................... 73
6.2 ENDOREDUPLICATIE ..................................................................................................................................................... 76
H7: CARCINOGENESE........................................................................................................................................................ 79
7.1 INTRODUCTIE - WAT IS KANKER?...................................................................................................................................... 79
7.2 DE MOLECULAIRE BIOLOGIE VAN KANKER........................................................................................................................... 79
7.3 CHEMICALIËN EN KANKER .............................................................................................................................................. 82
7.4 TESTEN VAN CHEMICALIËN OP KANKERVERWEKKEND POTENTIEEL ............................................................................................ 89
7.5 REPRESENTATIEVE MENSELIJKE CARCINOGENEN ................................................................................................................... 91
H8: FIGHT BACK................................................................................................................................................................ 94
8.1 TOXICOKINETISCHE RESPONS .......................................................................................................................................... 94
8.2 TOXICODYNAMISCHE RESPONS ........................................................................................................................................ 98
,
toxicologie
,
,H1: INTRODUCTIE TOT TOXICOLOGIE ................................................................................................................................. 1
1.1 DE COMPLEXITEIT VAN TOXICOLOGIE .................................................................................................................................. 1
1.2 HET ONTSTAAN VAN TOXICOLOGIE ..................................................................................................................................... 3
1.3 DOSIS-RESPONS ............................................................................................................................................................ 5
1.4 BRONNEN EN BEWEGING VAN TOXISCHE STOFFEN .................................................................................................................. 8
1.5 ECOTOXICOLOGIE .......................................................................................................................................................... 9
1.6 TOXICITEIT ................................................................................................................................................................. 11
H2: TOXICOKINETIEK – ADME .......................................................................................................................................... 13
2.1 INTRODUCTIE TOT TOXICOKINETIEK .................................................................................................................................. 13
2.2 ABSORPTIE ................................................................................................................................................................ 14
2.3 DISTRIBUTIE ............................................................................................................................................................... 23
2.4 ELIMINATIE – EXCRETIE ................................................................................................................................................. 26
H3: TOXICOKINETIEK – BIOTRANFORMATIE ..................................................................................................................... 28
3.1 INTRODUCTIE ............................................................................................................................................................. 28
3.2 CHEMISCHE AARD VAN GIFSTOFFEN .................................................................................................................................. 29
3.3 CHEMISCHE REACTIES ................................................................................................................................................... 29
3.4 BIOTRANSFORMATIEREACTIES ......................................................................................................................................... 29
3.5 BIOTRANSFORMATIEPLAATSEN ........................................................................................................................................ 36
3.6 FACTOREN DIE BIOTRANSFORMATIE BEÏNVLOEDEN ............................................................................................................... 37
3.7 SYNERGIE, ANTAGONISME EN CHEMISCHE INTERACTIES ......................................................................................................... 37
H4: OXIDATIEVE STRESS ................................................................................................................................................... 38
4.1 INLEIDING – WAT IS OXIDATIEVE STRESS? ........................................................................................................................... 38
4.2 ONTSTAAN VAN ZUURSTOF ............................................................................................................................................ 38
4.3 GEBRUIK VAN O2 DOOR ZOOGDIEREN ............................................................................................................................... 39
4.4 WAT VEROORZAAKT DE TOXISCHE EFFECTEN VAN O2? .......................................................................................................... 40
4.5 ANTIOXIDATIEVE VERDEDIGING ....................................................................................................................................... 44
4.6 OXIDATIEVE STRESS: SCHADE VS FUNCTIE ........................................................................................................................... 47
H5: CELSCHADE ................................................................................................................................................................ 52
5.1 INLEIDING.................................................................................................................................................................. 52
5.2 CELSCHADE: RECEPTOR-GEMEDIEERDE TOXICITEIT ............................................................................................................... 54
5.3 CELSCHADE: METABOLIET-AFHANKELIJKE TOXICITEIT ............................................................................................................. 58
5.4 MECHANISMS OF ACTION: HOE METABOLIETEN CELLEN BESCHADIGEN ...................................................................................... 61
5.5 HOE ZULLEN CELLEN HIEROP REAGEREN?........................................................................................................................... 72
5.6 MECHANISTISCHE TOXICOLOGIE IN HET ‘-OMICS’ TIJDPERK..................................................................................................... 72
H6: DE CELCYCLUS ............................................................................................................................................................ 73
6.1 DE KLASSIEKE CELCYCLUS ............................................................................................................................................... 73
6.2 ENDOREDUPLICATIE ..................................................................................................................................................... 76
H7: CARCINOGENESE........................................................................................................................................................ 79
7.1 INTRODUCTIE - WAT IS KANKER?...................................................................................................................................... 79
7.2 DE MOLECULAIRE BIOLOGIE VAN KANKER........................................................................................................................... 79
7.3 CHEMICALIËN EN KANKER .............................................................................................................................................. 82
7.4 TESTEN VAN CHEMICALIËN OP KANKERVERWEKKEND POTENTIEEL ............................................................................................ 89
7.5 REPRESENTATIEVE MENSELIJKE CARCINOGENEN ................................................................................................................... 91
H8: FIGHT BACK................................................................................................................................................................ 94
8.1 TOXICOKINETISCHE RESPONS .......................................................................................................................................... 94
8.2 TOXICODYNAMISCHE RESPONS ........................................................................................................................................ 98
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