Biomedical Science Department, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
J Biomed Mater Res A. 2009 Dec;91(3):786-94. doi: 10.1002/jbm.a.32290.
Polyhydroxyalkanoates (PHA) are naturally occurring biopolyesters that have great potential in the medical field. However, the leachables resulting from sterilization process of the biomaterials may exert toxic effect including genetic damage. Here, we demonstrate that although gamma-irradiation of poly(3-hydroxybutyrate-co-50 mol % 4-hydroxybutyrate) [P(3HB-co-4HB)] did not cause any change in the morphology by scanning electron microscopy, there was a significant degradation of this copolymer where the molecular weight was reduced by 37% after sterilization indicating the generation of leachables. Therefore, further investigation on the ability of the extract of this poststerilized copolymer to induce mutagenic effect was performed using Ames test (S. typhimurium strains TA1535 and TA1537) and umu test (S. typhimurium strain TA1535/pSK1002). Additionally, the capability of the extract to induce clastogenic effect was determined using Chinese hamster lung V79 fibroblast cells. Our results showed that with and without the presence of S9 metabolic activation, no mutagenic effects were observed in both Ames and umu tests when treated with P(3HB-co-4HB) extract. Similarly, treatment of P(3HB-co-4HB) extract in V79 fibroblast cells showed no significant production of micronuclei when compared with the positive control (Mitomycin C). Together, these results indicate that leachables of poststerilized P(3HB-co-4HB) cause no mutagenic and clastogenic effects.
聚羟基烷酸酯（PHA）是天然存在的生物聚酯，在医学领域具有巨大的潜力。然而，生物材料灭菌过程中产生的浸出物可能会产生毒性作用，包括遗传损伤。在这里，我们证明，尽管聚（3-羟基丁酸-co-50mol%4-羟基丁酸）[P（3HB-co-4HB）]的γ辐照不会通过扫描电子显微镜观察到形态发生任何变化，但这种共聚物存在明显的降解，其分子量在灭菌后降低了 37%，表明浸出物的产生。因此，使用艾姆斯试验（鼠伤寒沙门氏菌 TA1535 和 TA1537 株）和umu 试验（鼠伤寒沙门氏菌 TA1535/pSK1002 株）对这种经辐照后共聚物提取物诱导诱变作用的能力进行了进一步研究。此外，还使用中国仓鼠肺 V79 成纤维细胞测定了提取物诱导断裂作用的能力。我们的结果表明，无论是否存在 S9 代谢激活，用 P（3HB-co-4HB）提取物处理时，在艾姆斯和umu 试验中均未观察到诱变作用。同样，与阳性对照（丝裂霉素 C）相比，用 V79 成纤维细胞处理 P（3HB-co-4HB）提取物时，微核的产生没有显著增加。综上所述，这些结果表明，辐照后 P（3HB-co-4HB）的浸出物不会引起诱变和断裂作用。
