DNA损伤是指环境中物理或化学污染因素导致细胞内脱氧核糖核酸(DNA)结构发生改变。常见的致DNA损伤的化学物质包括亚硝胺类,在体内代谢分解后产生烷化剂——重氮烷,进而使DNA发生烷化作用,引起不可逆的变化而致癌;多环芳烃中的苯并(a)芘则在混合功能氧化酶的作用下形成具有亲电子结构的环氧化物,与细胞内大分子的亲核基团结合造成DNA损伤。若这种损伤无法修复或修复不彻底,则可能导致细胞癌变。某些金属如镍、铍和铬等致癌物质也可能与DNA残基形成稳定的复合物,产生致癌作用。
DNA损伤修复是指生物细胞内的脱氧核糖核酸(DNA)分子受损后结构恢复的现象,这一过程依赖于细胞内多种酶的作用。1968年,美国学者J·E·克利弗首次发现人类中的常染色体隐性遗传的光化癌变疾病——着色性干皮病是由基因突变导致的DNA损伤切除修复功能缺陷引起的。这一发现为恶性肿瘤的发生机制提供了重要的分子生物学证据,并使DNA损伤修复的研究进入医学领域。1979年,在莫斯科召开的第14届国际遗传学会议上,DNA损伤修复被列为重要议题之一,成为分子、遗传学和肿瘤学的重要研究课题。
DNA损伤的形式多样,常见的包括胸腺嘧啶二聚体的形成(主要由紫外线引起)、X射线或γ射线照射导致的DNA双链间氢键断裂以及单链或双链断裂;丝裂霉素C引起的DNA单链交联、碱基或核苷酸的变化等。DNA损伤修复的方式主要包括光复活、切补修复、复制后修复、适应性修复、链断裂修复及链交联修复等,这些研究有助于深入了解基因突变机制、衰老和癌变的原因,并应用于环境致癌因子的检测。
中文名称 | 英文名称 | CAS号 | 化学式 | 结构式图片 |
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非达霉素 | Fidaxomicin | 873857-62-6 | C52H74Cl2O18 |
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盐酸甲基苄肼 | matulane | 366-70-1 | C12H19N3O*ClH |
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白血病孤儿药 | vosaroxin | 175414-77-4 | C18H19N5O4S |
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甲基0328 | 3,4-dihydro-4-oxo-N-[(1S)-1-phenylethyl]-2-quinazolinepropanamide | 1445251-22-8 | C19H19N3O2 |
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瑞卡帕布(AG-014699) | AG-014699 | 459868-92-9 | C19H18FN3O*H3O4P |
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氨萘非特 | amonafide | 69408-81-7 | C16H17N3O2 |
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奥拉帕尼 | olaparib | 763113-22-0 | C24H23FN4O3 |
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奈达铂 | nedaplatin | 95734-82-0 | C2H8N2O3Pt |
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alpha-苯基-N-[2,2,2-三氯-1-[[[(4-氟-3-硝基苯基)氨基]硫代甲酰]氨基]乙基]-苯乙酰胺 | CGK-733 | 905973-89-9 | C23H18Cl3FN4O3S |
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YK 4-279; 4,7-二氯-1,3-二氢-3-羟基-3-[2-(4-甲氧基苯基)-2-氧代乙基]-2H-吲哚-2-酮 | YK-4-279 | 1037184-44-3 | C17H13Cl2NO4 |
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PJ34盐酸盐 | 2-(Dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide hydrochloride | 344458-15-7 | C17H18ClN3O2 |
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NU 7026; 2-(4-吗啉基)-4H-萘并[1,2-b]吡喃-4-酮 | 2-(morpholin-4-yl)benzo[h]chromen-4-one | 154447-35-5 | C17H15NO3 |
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ATM激酶抑制剂(CP-466722) | 1-(6,7-dimethoxyquinazolin-4-yl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-amine | 1080622-86-1 | C17H15N7O2 |
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AG 14361; 2-[4-[(二甲基氨基)甲基]苯基]-5,6-二氢咪唑并[4,5,1-jk][1,4]苯并二氮杂卓-7(4H)-酮 | AG14361 | 328543-09-5 | C19H20N4O |
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8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮 | 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one | 503468-95-9 | C25H19NO3S |
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7-硝基吲哚-2-甲酸 | 7-nitro-1H-indole-2-carboxylic acid | 6960-45-8 | C9H6N2O4 |
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5-(2-氧代-2-苯基乙氧基)-1(2H)-异喹啉酮 | 5-(2-Oxo-2-phenylethoxy)isoquinolin-1(2H)-one | 1048371-03-4 | C17H13NO3 |
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4-[4-氟-3-[(4-甲氧基哌啶-1-基)羰基]苄基]酞嗪-1(2H)-酮 | 4-[[4-fluoro-3-[(4-methoxy-1-piperidinyl)carbonyl]phenyl]methyl]-1(2H)-phthalazinone | 1174043-16-3 | C22H22FN3O3 |
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4-[4-[(3R)-3-甲基-4-吗啉基]-6-[1-(甲基磺酰基)环丙基]-2-嘧啶基]-1H-吲哚 | AZ 20 | 1233339-22-4 | C21H24N4O3S |
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3-硝基-4-碘苯甲酰胺 | 4-iodo-3-nitrobenzamide | 160003-66-7 | C7H5IN2O3 |
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3-氨基-6-[4-(甲基磺酰基)苯基]-N-苯基-2-吡嗪甲酰胺 | VE-821 | 1232410-49-9 | C18H16N4O3S |
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3-[3-[4-[(甲基氨基)甲基]苯基]-5-异恶唑基]-5-[4-[异丙磺酰基]苯基]-2-吡嗪胺 | VE822 | 1232416-25-9 | C24H25N5O3S |
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3,4-二氢-2,2-二甲基-2H-萘并[1,2-B]吡喃-5,6-二酮 | 2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione | 4707-32-8 | C15H14O3 |
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2-甲基-8-羟基-4-喹唑啉酮 | 8-hydroxy-2-methyl-4(3H)-quinazolinone | 90417-38-2 | C9H8N2O2 |
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2-氯-5-硝基-N-4-吡啶基苯甲酰胺 | T0070907 | 313516-66-4 | C12H8ClN3O3 |
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2-吗啉-4-基-6-噻蒽-1-基吡喃-4-酮 | 2-(4-morpholinyl)-6-(1-thianthrenyl)-4H-pyran-4-one | 587871-26-9 | C21H17NO3S2 |
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2-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸 | BIBR1532 | 321674-73-1 | C21H17NO3 |
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2-[2-氟-4-[(2S)-2-吡咯烷基]苯基]-1H-苯并咪唑-7-甲酰胺 | A-966492 | 934162-61-5 | C18H17FN4O |
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2-[(2R)-2-甲基-2-吡咯烷基]-1H-苯并咪唑-7-甲酰胺 | veliparib | 912444-00-9 | C13H16N4O |
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2-(4-甲基-1H-1,4-二氮杂环庚烷-1-基)-N-[(5-甲基-2-吡嗪基)甲基]-5-氧代-5H-苯并噻唑并[3,2-a][1,8]萘啶-6-甲酰胺 | CX-5461 | 1138549-36-6 | C27H27N7O2S |
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(8S,9R)-5-氟-8-(4-氟苯基)-2,7,8,9-四氢-9-(1-甲基-1H-1,2,4-三唑-5-基)-3H-吡啶并[4,3,2-DE]酞嗪-3-酮 | talazoparib | 1207456-01-6 | C19H14F2N6O |
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(2R,6S)-2,6-二甲基-N-[5-[6-(4-吗啉基)-4-氧代-4H-吡喃-2-基]-9H-噻吨-2-基]-4-吗啉乙酰胺 | KU-60019 | 925701-49-1 | C30H33N3O5S |
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—— | fidaxomicin | 873857-62-6 | C52H74Cl2O18 |
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—— | 2-(4-ethylpiperazin-1-yl)-N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yl)acetamide | 881375-00-4 | C33H34N4O4S |
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—— | Blasticidine S hydrochloride | 3513-03-9 | C17H27ClN8O5 |
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—— | Azanide;2-hydroxyacetic acid;platinum(2+) | 95734-82-0 | C2H8N2O3Pt |
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—— | [(2R,3S,4S,5S,6R)-6-[[(3Z,5Z,8S,9Z,11S,12R,13Z,15Z,18S)-12-[(2R,3S,4R,5S)-3,4-dihydroxy-6,6-dimethyl-5-(2-methylpropanoyloxy)oxan-2-yl]oxy-11-ethyl-8-hydroxy-18-[(1R)-1-hydroxyethyl]-9,13,15-trimethyl-2-oxo-1-oxacyclooctadeca-3,5,9,13,15-pentaen-3-yl]methoxy]-4-hydroxy-5-methoxy-2-methyloxan-3-yl] 3,5-dichloro-2-ethyl-4,6-dihydroxybenzoate | 873857-62-6 | C52H74Cl2O18 |
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—— | [(2R,3S,4S,5S,6R)-6-[[(3E,5Z,8S,9E,11S,12R,13E,15E,18S)-12-[(2R,3S,4R,5S)-3,4-dihydroxy-6,6-dimethyl-5-(2-methylpropanoyloxy)oxan-2-yl]oxy-11-ethyl-8-hydroxy-18-[(1R)-1-hydroxyethyl]-9,13,15-trimethyl-2-oxo-1-oxacyclooctadeca-3,5,9,13,15-pentaen-3-yl]methoxy]-4-hydroxy-5-methoxy-2-methyloxan-3-yl] 3,5-dichloro-2-ethyl-4,6-dihydroxybenzoate | 873857-62-6 | C52H74Cl2O18 |
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—— | Azanide;2-oxidoacetate;platinum(4+) | 95734-82-0 | C2H6N2O3Pt |
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—— | 2-Oxidoacetate;platinum(2+) | 95734-82-0 | C2H2O3Pt |
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—— | flupirtine maleate | 75507-68-5 | C4H4O4*C15H17FN4O2 |
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—— | Blasticidine S HCl | 3513-03-9 | C17H27ClN8O5 |
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—— | [6-[[12-[3,4-dihydroxy-6,6-dimethyl-5-(2-methylpropanoyloxy)oxan-2-yl]oxy-11-ethyl-8-hydroxy-18-(1-hydroxyethyl)-9,13,15-trimethyl-2-oxo-1-oxacyclooctadeca-3,5,9,13,15-pentaen-3-yl]methoxy]-4-hydroxy-5-methoxy-2-methyloxan-3-yl] 3,5-dichloro-2-ethyl-4,6-dihydroxybenzoate | 873857-62-6 | C52H74Cl2O18 |
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