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[1] µ¶¼ºÇÐÀÇ ºÐÀÚ£»ýÈÇÐÀû ¿ø¸®¿Í Central dogma 1. µ¶¼ºÇÐÀÇ ºÐÀÚ£»ýÈÇÐÀû ¿ø¸®¿Í Central dogma 2. µ¶¼º¹ßÇöÀ» À§ÇÑ ÈÇаáÇÕ ¹× ÈÇÐÀû Ư¼º 3. À¯±âÈÇй°Áú°ú µ¶¼º¹°ÁúÀÇ °³³ä°ú ºÐ·ù 4. BiotransformationÀÇ °³³ä
[2] Á¦1»ó¹ÝÀÀ(Phase I reaction)£Cytochrome P450£ÀÇÁ¸¼º »ýüÀüȯ 1. Cytochrome P450ÀÇ ¹ß°ß°ú ºÐ·ù 2. Cytochrome P450ÀÇ ±¸Á¶(topology)¿Í ±âÁúƯÀ̼º 3. P450ÀÇ ºÐÆ÷ÇÏ´Â Á¶Á÷, ¼¼Æ÷ ±×¸®°í ¼¼Æ÷¼Ò±â°ü¿¡ ÀÖ¾î¼ Æ¯À̼º(specificity) 4. Cytochrome P450ÀÇ Ã˸ŹÝÀÀ »çÀÌŬ(catalytic cycle) 5. P450¿¡ ÀÇÇÑ 4°¡Áö ÁÖ¿ä Ã˸ŹÝÀÀ 6. P450 À¯ÀüÀÚ ¹× À¯µµ±âÀü(induction mechanism) 7. P450ÀÇ È°¼ºÀúÇرâÀü 8. Toxicants£drug metabolism enzyme families: CYP1, 2, 3 9. Extrahepatic tissues¿¡¼ÀÇ P450 ¹ßÇö£CYP1, CYP2¿Í CYP3 °è¿ 10. P450ÀÇ À¯µµ°³½Ã¿Í È¿¼ÒºÐÇØ
[3] Á¦1»ó¹ÝÀÀ(Phase 1 reaction)£Cytochrome P450 ¿ÜÀÇ ÁÖ¿ä È¿¼Ò¿¡ ÀÇÇÑ »ýüÀüȯ 1. Flavin mono£oxygenase 2. Epoxide hydrolase 3. Monoamine oxidase 4. Alcohol dehydrogenase¿Í acetaldehyde dehydrogenase µîÀ» ºñ·ÔÇÑ ¿¡Åº¿Ã ºÐÇØ È¿¼Ò 5. Quinone reductase 6. Xanthine oxidoreductase
[4] Á¦2»ó¹ÝÀÀ(Phase 2 reaction)¿¡ ÀÇÇÑ »ýüÀüȯ 1. Glucuronic acid conjugation 2. Sulfate conjugation 3. Acetylation conjugation 4. Methylation 5. Amino acid conjugation 6. GSHÆ÷ÇÕ¹ÝÀÀ 7. Á¦1»ó¹ÝÀÀ ¹× Á¦2»ó¹ÝÀÀÀÇ gene£coordinate regulation
[5] »ýüȰ¼ºÈ(Bioactivation)£Reactive intermediates 1. Reactive intermediates£Electrophilic metabolites 2. Carbon£centered radical°ú Redox£active species
[6] µ¶¹°µ¶·ÂÇÐ(Toxicodynamics)£Reactive intermediates¿Í DNA, ÁöÁú, ´Ü¹éÁú µî°úÀÇ »óÈ£ÀÛ¿ë 1. È°¼ºÁß°£´ë»çü¿¡ ÀÇÇÑ DNA ¼Õ»ó 2. È°¼ºÁß°£´ë»çü¿¡ ÀÇÇÑ ´Ü¹éÁú ¹× ÁöÁú ¼Õ»ó
[7] ÈÇÐÀû ¹ß¾ÏÈ(Chemical carcinogenesis) 1. ¹ß¾ÏÀÇ multistage theory 2. ¹ß¾ÏÈ¿¡ ´ëÇÑ ½ÉÃþÀû ÀÌÇØ
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ÀÌ Ã¥ "µ¶¼ºÇÐÀÇ ºÐÀÚ£»ýÈÇÐÀû ¿ø¸®"´Â ü³»¿¡¼ À¯±â¹°ÁúÀÇ µ¶¼ºÀ¯¹ß¿¡ ÀÖ¾î¼ ±âº»¿ø¸®¿¡ ´ëÇÑ ÀÌÇظ¦ À§ÇÏ¿© ºÐÀÚ»ý¹°ÇÐ ¹× »ýÈÇÐ Ãø¸é¿¡¼ Á¢±ÙÇÏ°í ÀÖ´Ù. IARC(±¹Á¦¾Ï¿¬±¸¼Ò)ÀÇ ÀÎü¹ß¾Ï¹°Áú ºÐ·ù¿¡ µû¸£¸é 61Á¾ÀÇ ÀÎü¹ß¾Ï¹°Áú Áß 90% ÀÌ»óÀÌ À¯±â¹°ÁúÀ̶ó°í ÇÑ´Ù. ÀÌ·Î º¸¾Æ À¯±â¹°ÁúÀÌ ¹«±â¹°Áúº¸´Ù µ¶¼ºÇÐÀû Ãø¸é¿¡¼ ´õ ½É°¢ÇÑ °Ç°À§Çظ¦ Áشٰí ÇÒ ¼ö ÀÖÀ» °ÍÀÌ´Ù. ¶ÇÇÑ »ê¾÷Àû, ȯ°æÀû ¶Ç´Â °³ÀÎ ½À°üÀû °æ·Î¸¦ ÅëÇØ ³ëÃâµÇ´Â ÈÇй°Áú Áß À¯±â¹°ÁúÀÌ º¸´Ù ´õ Å« ºñÁßÀ» Â÷ÁöÇÏ´Â °Íµµ »ç½ÇÀÌ´Ù.
ÀúÀÚ´Â ºÐÀÚ»ý¹°ÇÐÀÇ ÇÙ½ÉÀ» °£´ÜÈ÷ ¼³¸íÇÏ´Â µ¥ ÀÖ¾î¼ 'Central dogma(Áß½ÉÀÌ·Ð)'°¡ °¡Àå ¸¹ÀÌ ÀÌ¿ëµÇ°í ÀÖ°í À¯±â¹°Áú¿¡ ´ëÇÑ µ¶¼ºÇÐÀÇ ºÐÀÚ£»ýÈÇÐÀû ¿ø¸®´Â 'Central dogma'¿¡ ´ëÇÑ ÀÌÇØÀ̸ç ÀÌ´Â ´ëºÎºÐ À¯±âÈÇй°ÁúÀÇ °øÅëÀûÀÎ µ¶¼º±âÀüÀ¸·Î °í·ÁÇÒ ¼ö ÀÖ´Ù°í ¸»ÇÑ´Ù. ¿ªÀ¸·Î µ¶¼ºÇÐÀÇ ºÐÀÚ£»ýÈÇÐÀû ¿ø¸®¿¡ ´ëÇÑ Á¢±ÙÀº µ¶¼º¹°ÁúÀÇ Ã¼³» µ¿ÅÂ¿Í °ü·ÃµÈ È¿¼ÒÀÇ È°¼º°ú ÀúÇØ¿¡ ´ëÇÑ ÀÌÇظ¦ À§ÇÑ °ÍÀÌ¸ç ¶ÇÇÑ À̸¦ ÅëÇØ »õ·Î¿î ¾à¹° ¹× ±â´É¼º½ÄÇ°ÀÇ °³¹ß¿¡ ÀÀ¿ëµÇ±æ ¹Ù¶ó´Â ¸¶À½À¸·Î Àú¼úÇÏ¿´À½À» ¹àÈ÷°í ÀÖ´Ù.
ÀÌ Ã¥ÀÇ 1Àå¿¡¼´Â Central dogmaÀÇ ÀÌÇØ¿Í µ¶¼º¹ßÇöÀ» ÈÇÐÀû Ư¼º, µ¶¼º¹°ÁúÀÇ °³³ä°ú ºÐ·ù¿¡ ´ëÇØ ¼³¸íÇÑ´Ù. 2Àå¿¡¼´Â Á¦1»ó¹ÝÀÀ(phase 1)£Cytochrome P450£ÀÇÁ¸¼º »ýüÀüȯ¿¡ ´ëÇØ ¸»ÇÏ°í 3ÀåÀº Á¦1»ó¹ÝÀÀ(Phase 1 reaction)£Cytochrome P450 ¿ÜÀÇ ÁÖ¿ä È¿¼Ò¿¡ ÀÇÇÑ »ýüÀüȯ, 4Àå¿¡¼´Â Á¦2»ó¹ÝÀÀ(Phase 2 reaction)¿¡ ÀÇÇÑ »ýüÀüȯ¿¡ ´ëÇØ ¼³¸íÇÑ´Ù. 5ÀåÀÇ ÁÖÁ¦´Â »ýüȰ¼ºÈ(Bioactivation)ÀÌ°í 6Àå¿¡¼´Â µ¶¹°µ¶·ÂÇÐ(Toxicodynamics)£Reactive intermediates¿Í DNA, ÁöÁú, ´Ü¹éÁú µî°úÀÇ »óÈ£ÀÛ¿ë¿¡ ´ëÇØ »ó¼¼È÷ ¹àÈù´Ù. 7ÀåÀÇ ÁÖÁ¦´Â ÈÇÐÀû¹ß¾Ï(Chemical carcinogenesis)À¸·Î ¾Ï¼¼Æ÷¿¡ ´ëÇÑ ÈÇÐÀû ¼³¸íÀÌ´Ù.
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