DNA損傷是指環(huán)境中物理或化學(xué)污染因素導(dǎo)致細(xì)胞內(nèi)脫氧核糖核酸(DNA)結(jié)構(gòu)發(fā)生改變。常見的致DNA損傷的化學(xué)物質(zhì)包括亞硝胺類,在體內(nèi)代謝分解后產(chǎn)生烷化劑——重氮烷,進(jìn)而使DNA發(fā)生烷化作用,引起不可逆的變化而致癌;多環(huán)芳烴中的苯并(a)芘則在混合功能氧化酶的作用下形成具有親電子結(jié)構(gòu)的環(huán)氧化物,與細(xì)胞內(nèi)大分子的親核基團(tuán)結(jié)合造成DNA損傷。若這種損傷無法修復(fù)或修復(fù)不徹底,則可能導(dǎo)致細(xì)胞癌變。某些金屬如鎳、鈹和鉻等致癌物質(zhì)也可能與DNA殘基形成穩(wěn)定的復(fù)合物,產(chǎn)生致癌作用。
DNA損傷修復(fù)是指生物細(xì)胞內(nèi)的脫氧核糖核酸(DNA)分子受損后結(jié)構(gòu)恢復(fù)的現(xiàn)象,這一過程依賴于細(xì)胞內(nèi)多種酶的作用。1968年,美國學(xué)者J·E·克利弗首次發(fā)現(xiàn)人類中的常染色體隱性遺傳的光化癌變疾病——著色性干皮病是由基因突變導(dǎo)致的DNA損傷切除修復(fù)功能缺陷引起的。這一發(fā)現(xiàn)為惡性腫瘤的發(fā)生機(jī)制提供了重要的分子生物學(xué)證據(jù),并使DNA損傷修復(fù)的研究進(jìn)入醫(yī)學(xué)領(lǐng)域。1979年,在莫斯科召開的第14屆國際遺傳學(xué)會議上,DNA損傷修復(fù)被列為重要議題之一,成為分子、遺傳學(xué)和腫瘤學(xué)的重要研究課題。
DNA損傷的形式多樣,常見的包括胸腺嘧啶二聚體的形成(主要由紫外線引起)、X射線或γ射線照射導(dǎo)致的DNA雙鏈間氫鍵斷裂以及單鏈或雙鏈斷裂;絲裂霉素C引起的DNA單鏈交聯(lián)、堿基或核苷酸的變化等。DNA損傷修復(fù)的方式主要包括光復(fù)活、切補修復(fù)、復(fù)制后修復(fù)、適應(yīng)性修復(fù)、鏈斷裂修復(fù)及鏈交聯(lián)修復(fù)等,這些研究有助于深入了解基因突變機(jī)制、衰老和癌變的原因,并應(yīng)用于環(huán)境致癌因子的檢測。
| 中文名稱 | 英文名稱 | CAS號 | 化學(xué)式 |
|---|---|---|---|
| 非達(dá)霉素 | Fidaxomicin | 873857-62-6 | C52H74Cl2O18 |
| 鹽酸甲基芐肼 | matulane | 366-70-1 | C12H19N3O*ClH |
| 白血病孤兒藥 | vosaroxin | 175414-77-4 | C18H19N5O4S |
| 甲基0328 | 3,4-dihydro-4-oxo-N-[(1S)-1-phenylethyl]-2-quinazolinepropanamide | 1445251-22-8 | C19H19N3O2 |
| 瑞卡帕布(AG-014699) | AG-014699 | 459868-92-9 | C19H18FN3O*H3O4P |
| 滅瘟素S鹽酸鹽 | blasticidin S hydrochloride | 3513-03-9 | C17H26N8O5*ClH |
| 氨萘非特 | amonafide | 69408-81-7 | C16H17N3O2 |
| 奧拉帕尼 | olaparib | 763113-22-0 | C24H23FN4O3 |
| 奈達(dá)鉑 | nedaplatin | 95734-82-0 | C2H8N2O3Pt |
| 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 |
| YK 4-279; 4,7-二氯-1,3-二氫-3-羥基-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 |
| PJ34鹽酸鹽 | 2-(Dimethylamino)-N-(6-oxo-5,6-dihydrophenanthridin-2-yl)acetamide hydrochloride | 344458-15-7 | C17H18ClN3O2 |
| NU 7026; 2-(4-嗎啉基)-4H-萘并[1,2-b]吡喃-4-酮 | 2-(morpholin-4-yl)benzo[h]chromen-4-one | 154447-35-5 | C17H15NO3 |
| ATM激酶抑制劑(CP-466722) | 1-(6,7-dimethoxyquinazolin-4-yl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-amine | 1080622-86-1 | C17H15N7O2 |
| AG 14361; 2-[4-[(二甲基氨基)甲基]苯基]-5,6-二氫咪唑并[4,5,1-jk][1,4]苯并二氮雜卓-7(4H)-酮 | AG14361 | 328543-09-5 | C19H20N4O |
| 8-(4-二苯并噻吩基)-2-(4-嗎啉基)-4H-1-苯并吡喃-4-酮 | 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one | 503468-95-9 | C25H19NO3S |
| 7-硝基吲哚-2-甲酸 | 7-nitro-1H-indole-2-carboxylic acid | 6960-45-8 | C9H6N2O4 |
| 5-(2-氧代-2-苯基乙氧基)-1(2H)-異喹啉酮 | 5-(2-Oxo-2-phenylethoxy)isoquinolin-1(2H)-one | 1048371-03-4 | C17H13NO3 |
| 4-[4-氟-3-[(4-甲氧基哌啶-1-基)羰基]芐基]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-[(3R)-3-甲基-4-嗎啉基]-6-[1-(甲基磺酰基)環(huán)丙基]-2-嘧啶基]-1H-吲哚 | AZ 20 | 1233339-22-4 | C21H24N4O3S |
| 3-硝基-4-碘苯甲酰胺 | 4-iodo-3-nitrobenzamide | 160003-66-7 | C7H5IN2O3 |
| 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-[3-[4-[(甲基氨基)甲基]苯基]-5-異惡唑基]-5-[4-[異丙磺酰基]苯基]-2-吡嗪胺 | VE822 | 1232416-25-9 | C24H25N5O3S |
| 3,4-二氫-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 |
| 2-甲基-8-羥基-4-喹唑啉酮 | 8-hydroxy-2-methyl-4(3H)-quinazolinone | 90417-38-2 | C9H8N2O2 |
| 2-氯-5-硝基-N-4-吡啶基苯甲酰胺 | T0070907 | 313516-66-4 | C12H8ClN3O3 |
| 2-嗎啉-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-[[(2E)-3-(2-萘基)-1-氧代-2-丁烯基]氨基]苯甲酸 | BIBR1532 | 321674-73-1 | C21H17NO3 |
| 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-[(2R)-2-甲基-2-吡咯烷基]-1H-苯并咪唑-7-甲酰胺 | veliparib | 912444-00-9 | C13H16N4O |
| 2-(4-甲基-1H-1,4-二氮雜環(huán)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 |
| (8S,9R)-5-氟-8-(4-氟苯基)-2,7,8,9-四氫-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 |
| (2R,6S)-2,6-二甲基-N-[5-[6-(4-嗎啉基)-4-氧代-4H-吡喃-2-基]-9H-噻噸-2-基]-4-嗎啉乙酰胺 | KU-60019 | 925701-49-1 | C30H33N3O5S |
| —— | fidaxomicin | 873857-62-6 | C52H74Cl2O18 |
| —— | 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 |
| —— | Blasticidine S hydrochloride | 3513-03-9 | C17H27ClN8O5 |
| —— | Azanide;2-hydroxyacetic acid;platinum(2+) | 95734-82-0 | C2H8N2O3Pt |
| —— | [(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-[[(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 |
| —— | Azanide;2-oxidoacetate;platinum(4+) | 95734-82-0 | C2H6N2O3Pt |
| —— | 2-Oxidoacetate;platinum(2+) | 95734-82-0 | C2H2O3Pt |
| —— | flupirtine maleate | 75507-68-5 | C4H4O4*C15H17FN4O2 |
| —— | Blasticidine S HCl | 3513-03-9 | C17H27ClN8O5 |
| —— | [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 |