CAJ | 학술논문

目的：研究乙二胺为核心的PAMAM树枝状聚合物(5.0代)纳米材料溶液的遗传毒性。方法：采用Ames试验平板掺入法，设3985、797、139.4、31.88和6.376μg/皿的5个乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液浓度组，在加与不加S9混合液的条件下观察回变菌落数。同时采用L5178Y细胞胞质分裂阻滞微核细胞组学试验，给予受试细胞终浓度分别为0.625、1.25、2.5、5、10μg/mL的受试物，观察其微核组效应、剂量-效应和时间-效应关系。结果：受试物溶液各剂量组均未引起测试菌株回变菌落数明显增加，Ames试验结果为阴性。胞质分裂阻滞微核细胞组学试验中，与阴性对照组比较，1.25μg/mL的受试物即可诱导受试细胞出现核芽(P<0.01)；2.5μg/mL及以上剂量可进一步诱使细胞出现总微核、Ⅰ型微核、Ⅱ型微核和核质桥效应(P<0.01)，且存在明显的剂量-效应关系(除核质桥外，r值均>0.5，P均<0.05)。与阴性对照组比较，在5μg/mL剂量下，乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液在9 h时即可诱导受试细胞的总微核、Ⅰ型微核、Ⅱ型微核和核芽增加(P<0.01)；在18 h时出现核质桥数增加(P<0.01)，各项指标在27 h达到峰值。结论：乙二胺为核心的PAMAM树枝状聚合物(5.0代)溶液对鼠伤寒沙门氏菌无致基因突变作用；对L5178Y细胞可诱导4类微核组效应，并有明显的剂量-效应和时间-效应关系；从剂量和时间来看，以核芽效应最为敏感。
목적：연구을이알위핵심적PAMAM수지상취합물(5.0대)납미재료용액적유전독성。방법：채용Ames시험평판참입법，설3985、797、139.4、31.88화6.376μg/명적5개을이알위핵심적PAMAM수지상취합물(5.0대)용액농도조，재가여불가S9혼합액적조건하관찰회변균락수。동시채용L5178Y세포포질분렬조체미핵세포조학시험，급여수시세포종농도분별위0.625、1.25、2.5、5、10μg/mL적수시물，관찰기미핵조효응、제량-효응화시간-효응관계。결과：수시물용액각제량조균미인기측시균주회변균락수명현증가，Ames시험결과위음성。포질분렬조체미핵세포조학시험중，여음성대조조비교，1.25μg/mL적수시물즉가유도수시세포출현핵아(P<0.01)；2.5μg/mL급이상제량가진일보유사세포출현총미핵、Ⅰ형미핵、Ⅱ형미핵화핵질교효응(P<0.01)，차존재명현적제량-효응관계(제핵질교외，r치균>0.5，P균<0.05)。여음성대조조비교，재5μg/mL제량하，을이알위핵심적PAMAM수지상취합물(5.0대)용액재9 h시즉가유도수시세포적총미핵、Ⅰ형미핵、Ⅱ형미핵화핵아증가(P<0.01)；재18 h시출현핵질교수증가(P<0.01)，각항지표재27 h체도봉치。결론：을이알위핵심적PAMAM수지상취합물(5.0대)용액대서상한사문씨균무치기인돌변작용；대L5178Y세포가유도4류미핵조효응，병유명현적제량-효응화시간-효응관계；종제량화시간래간，이핵아효응최위민감。
OBJECTIVE:To study the genotoxicity of PAMAM dendrimer (ethylenediamine core) generation 5.0 solution.METHODS:In the plate incorporation test ofSalmonella typhimurium,the average colony number of spontaneous revertants of TA97,TA98,TA100,TA102,TA1535 were set at 5 concentrations:3 985,797,139.4, 31.88 and6.376μg per plate. In the cytokinesis-block micronucleus cytome(CBMN Cyt) assay,the final concentration 0.625,1.25,2.5,5,10μg/mL of PAMAM dendrimer (ethylenediamine core) generation 5.0 wasadded to L5178Y cells,then assessed the micronucleus cytome effect,dose-effect and time-effect relationships.RESULTS: The colony number of revertants for the materials tested did not obviously increase,compared with that of spontaneous revertants. The result of Ames test for the subject was negative. In the CBMN Cyt assay,the frequency of nuclear buds increased at concentration of 1.25μg/mL.The formation of total,type Ⅰ andtypeⅡ micronuclei as well as nuclear-cytoplasmic bridges were oberservedat andabove concentration of 2.5μg/mL. At of 5μg/mL,the time-effect results indicated that the number of total,type Ⅰ amdtype Ⅱ micronuclei and nuclear buds increased at 9 h,while the nucleoplasmic bridges started to increase at 18h. The indexes of total,type Ⅰandtype Ⅱ micronuclei,nucleoplasmic bridges and nuclear buds reached their peak at 27 h.CONCLUSION:The PAMAM dendrimer (ethylenediamine core) generation 5.0 solution showed no potential mutagenicity. While could cause four kinds of micronucleus cytome effects with clear dose-effect and time-effect in L5178Y cells. From the dose and time point of view,nuclear bud was the most sensitive index.