| Summary: | 碩士 === 中國醫藥學院 === 環境醫學研究所 === 88 === Styrene is widely used in the production of plastics. It is metabolic activated by cytochrome P-450 to styrene-7, 8 -oxide (SO) with two enantiomeric isomers, R-SO and S-SO. SO is a known animal carcinogen and probable human carcinogen. It is unclear which isomer plays a more important role in SO-induced cytotoxicity and mutagenicity.
In this study the cytotoxicity and mutagenicity of R-SO, S-SO and racemic styrene oxide ((R+S)-SO) were determined in the human lymphoblastoid cell line (TK6). After exposure to various concentrations (60~180μM) of SO and its isomers for 24 hours, treated cells were counted and plated to determine the relative survival (RS) by the growth delay curve and the plating efficiency (PE)measurement, respectively. SO and SO isomers were cytotoxic to TK6 cells in a dose-dependent manner. The RS of 120μM R-SO,S-SO and (R+S)-SO-treated cells were 50.6, 56.3 and 51.2%, respectively. At 180μM R-SO,S-SO and (R+S)-SO-treated cells were 12.7 14.0 and 14.0%, respectively. However, there is no statistically significant difference among SO and its optical isomer-induced cytotoxicity.
The relative mutagenic potential of the SO and its isomers was determined at hypoxanthine guanine phosphoribosyl-transferase (hprt) and thymidine kinase (tk) gene in TK6 cells. The mutant frequencies at the hprt and tk gene induced by SO and its isomers were dose-dependent. S-SO was more mutatgenic at hprt gene than R-SO (p<0.05). Treatment of 120μM R-SO, S-SO and (R+S)-SO induced the hprt gene mutation frequencies of 26.6, 32.96 and 35.1 ×10-6, respectively. Treatment of 180μM R-SO, S-SO and (R+S)-SO induced hprt gene mutation frequency of 32.1, 50.0 and 45.0 ×10-6, respectively. Treatment of 120μM R-SO, S-SO and (R+S)-SO induced tk-fast mutant frequency of 31.0, 23.1 and 28.3×10-6, respectively. Treatment of 120μM R-SO, S-SO and (R+S)-SO induced tk-slow mutant frequency of 28.0, 41.1 and 31.7×10-6, respectively. No statistically significant difference among R-SO, S-SO and (R+S)-SO-induced tk-fast and tk-slow mutant frequencies was found.
Results of this study show SO and SO optical induced cytotoxicity and mutagenicity in a dose dependent relationship, but they were not significal. Taken together, these data suggest that R-SO and S-SO may play a similar important role in (R+S)-SO-induced cytotoxicity and mutagenicity.
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