关键词: 树枝状聚合物, Ames试验, 遗传毒性, 微核组学效应

Abstract:

OBJECTIVE: To study the genotoxicity of PAMAM dendrimer (ethylenediamine core) generation 5.0 solution. METHODS:In the plate incorporation test of Salmonella 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 and 6.376 μg per plate. In the cytokinesis-block micronucleus cytome(CBMN Cyt) assay, the final concentration 0.625, 1.25, 2.5, 5, 10 μg/mL of PAMAM dendrimer (ethylenediamine core) generation 5.0 was added 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 1.25 μg/mL. The formation of total, type Ⅰ and typeⅡ micronuclei as well as nuclear-cytoplasmic bridges were oberserved at and above concentration of 2.5 μg/mL. At of 5 μg/mL, the time-effect results indicated that the number of total, type Ⅰ amd type Ⅱ micronuclei and nuclear buds increased at 9 h, while the nucleoplasmic bridges started to increase at 18h. The indexes of total, type Ⅰ and type 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.

Key words: dendrimers, Ames test, genotoxicity, micronucleus genomic effect