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DNA损伤(DNA Damage)

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
非达霉素 Fidaxomicin 873857-62-6 C52H74Cl2O18
非达霉素
盐酸甲基苄肼 matulane 366-70-1 C12H19N3O*ClH
盐酸甲基苄肼
白血病孤儿药 vosaroxin 175414-77-4 C18H19N5O4S
白血病孤儿药
甲基0328 3,4-dihydro-4-oxo-N-[(1S)-1-phenylethyl]-2-quinazolinepropanamide 1445251-22-8 C19H19N3O2
甲基0328
瑞卡帕布(AG-014699) AG-014699 459868-92-9 C19H18FN3O*H3O4P
瑞卡帕布(AG-014699)
氨萘非特 amonafide 69408-81-7 C16H17N3O2
氨萘非特
奥拉帕尼 olaparib 763113-22-0 C24H23FN4O3
奥拉帕尼
奈达铂 nedaplatin 95734-82-0 C2H8N2O3Pt
奈达铂
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
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
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
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
PJ34盐酸盐 2-(Dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide hydrochloride 344458-15-7 C17H18ClN3O2
PJ34盐酸盐
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
NU 7026; 2-(4-吗啉基)-4H-萘并[1,2-b]吡喃-4-酮
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
ATM激酶抑制剂(CP-466722)
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
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
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
8-(4-二苯并噻吩基)-2-(4-吗啉基)-4H-1-苯并吡喃-4-酮
7-硝基吲哚-2-甲酸 7-nitro-1H-indole-2-carboxylic acid 6960-45-8 C9H6N2O4
7-硝基吲哚-2-甲酸
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
5-(2-氧代-2-苯基乙氧基)-1(2H)-异喹啉酮
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
4-[4-氟-3-[(4-甲氧基哌啶-1-基)羰基]苄基]酞嗪-1(2H)-酮
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
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
3-硝基-4-碘苯甲酰胺 4-iodo-3-nitrobenzamide 160003-66-7 C7H5IN2O3
3-硝基-4-碘苯甲酰胺
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
3-氨基-6-[4-(甲基磺酰基)苯基]-N-苯基-2-吡嗪甲酰胺
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
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
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
3,4-二氢-2,2-二甲基-2H-萘并[1,2-B]吡喃-5,6-二酮
2-甲基-8-羟基-4-喹唑啉酮 8-hydroxy-2-methyl-4(3H)-quinazolinone 90417-38-2 C9H8N2O2
2-甲基-8-羟基-4-喹唑啉酮
2-氯-5-硝基-N-4-吡啶基苯甲酰胺 T0070907 313516-66-4 C12H8ClN3O3
2-氯-5-硝基-N-4-吡啶基苯甲酰胺
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
2-吗啉-4-基-6-噻蒽-1-基吡喃-4-酮
2-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸 BIBR1532 321674-73-1 C21H17NO3
2-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸
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
2-[2-氟-4-[(2S)-2-吡咯烷基]苯基]-1H-苯并咪唑-7-甲酰胺
2-[(2R)-2-甲基-2-吡咯烷基]-1H-苯并咪唑-7-甲酰胺 veliparib 912444-00-9 C13H16N4O
2-[(2R)-2-甲基-2-吡咯烷基]-1H-苯并咪唑-7-甲酰胺
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
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
(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
(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
(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
(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
—— fidaxomicin 873857-62-6 C52H74Cl2O18
fidaxomicin
—— 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
2-(4-ethylpiperazin-1-yl)-N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thiophen-1-yl)acetamide
—— Blasticidine S hydrochloride 3513-03-9 C17H27ClN8O5
Blasticidine S hydrochloride
—— Azanide;2-hydroxyacetic acid;platinum(2+) 95734-82-0 C2H8N2O3Pt
Azanide;2-hydroxyacetic acid;platinum(2+)
—— [(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
[(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
—— [(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
[(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
—— Azanide;2-oxidoacetate;platinum(4+) 95734-82-0 C2H6N2O3Pt
Azanide;2-oxidoacetate;platinum(4+)
—— 2-Oxidoacetate;platinum(2+) 95734-82-0 C2H2O3Pt
2-Oxidoacetate;platinum(2+)
—— flupirtine maleate 75507-68-5 C4H4O4*C15H17FN4O2
flupirtine maleate
—— Blasticidine S HCl 3513-03-9 C17H27ClN8O5
Blasticidine S HCl
—— [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
[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