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報.
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圖1. 180μM SO 與 SO 光學異構物誘發 TK6 細胞 之生長遲緩現象
0 5 10 15 20 25 30
0 1 2 3
D A Y
RCN (Fold)
R
S
R + S
control
圖 2.以 細 胞 相 對 存 活 率（ RCN）評 估 SO 與 SO 光 學 異 構物對 TK6 細胞之毒性
0 20 40 60 80 100 120 140
60 120 160 180
dose (μM)
Relative surviva (%)
R
S
R+S
圖 3. 以 細 胞 群 落 形 成 能 力（ PE）評估 SO 與 SO 光 學 異 構 物 對 TK6 細胞之毒性
0 20 40 60 80 100 120
60 120 160 180
dose (μM)
Relative survival (%)
R
S
R+S
圖4. SO 與 SO 光學異構物在 TK6 細胞誘發 hprt 突變率
0 10 20 30 40 50 60 70
0 60 120 180
dose(μM)
hprt MUTANT FREQUENCY (X 10
-6) R
S
R+S
圖 5 SO 與 SO 光學異構物在 TK6 細胞誘發 tk fast 基因突變率
0 10 20 30 40 50 60
0 60 120 160 180
dose (μM)
tk MUTANT FREQUENCY (X 10 -6 )R S R+S
圖 6. SO 與 SO 光學異構物對在 TK6 細胞誘發 tk total 因突變率
0 20 40 60 80 100 120 140
0 60 120 160 180
dose (μM) tk MUTANT FREQUENCY (X 10 -6 )
R S R＋S
圖 7 SO 與 SO 光學異構物對在 TK6 細胞誘發 tk slow 基因突變率
0 20 40 60 80 100 120
0 60 120 160 180
dose(μM)
tk MUTANT FREQUENCY (X 10 -6 ) R
S R+S
表 1. SO 與 SO 光學異構物對 TK6 細胞之致突變率
R-SO S-SO (R+S)-SO Dose
(μM) Mutant Frequencies (X10-6)
Hprt 基因
control 8.86 9.31 11.05
60 16.68 21.83 26.1
120 26.56 32.96 35.03
180 32.08 50.04 45.03
tk-fast
control 7.25 9.50 9.30
60 19.33 14.05 14.25
120 23.05 30.95 28.33
180 33.67 34.64 44.08
tk-slow
control 7.55 9.71 15.98
60 30.86 22.25 30.81
120 41.07 28.01 31.72
180 89.52 66.04 78.18
tk-total
control 12.23 17.53 20.65
60 46.68 33.80 45.10
120 64.13 55.17 57.80
180 123.58 87.84 119.50
(A)
(B) (C)
α β
附圖 1 SO 與 SO 光學異構物之化學結構
（A）styrene (B)R-SO （C）S-SO
CH C
H H
CH CH 2 H O
O
CH 2 CH
H
51
styrene glycol mandelic acid 附圖 2. Styrene 之活化與去活化路徑
SO ((R+S)-SO)
glutathione S-transferases
(GST)
Epoxide hydrolase
(EH)
mercapturic acid
DNA adduct
Mutation Styrene
CYP-450
1 2 3
5’-C GGA CAA GAA G-3’
60 61 62
S-isomer R-isomer
附 圖 3.
SO 光 學 異 構 物 與 人 類 N-ras 基 因 codon 61 上之 adenine 中 N7 位置形成之
DNA adduct
（Latham et al.,1993）C CH2 NH
H
N N
N
N
N N
N
N
C CH2 H
NH
OH OH
53
附圖 4. 測量細胞毒性與突變率之實驗流程
人 類 淋 巴 母 細 胞 (T K 6 )經 C H A T 處 理 7 2 小 時
去 除 C H A T 後 ， 繼 續 培 養 3 - 4 天 以 R - S O 、 S - S O 或 S O 處 理 2 4 小 時
以 正 常 培 養 基 培 養 立 刻 接 種 於 9 6 w e l l p l a t e
以 細 胞 群 落 (c o l o n y ) 數 目 計 算 細 胞 相 對 毒 性 （ R S ） 接 種 於 含
6 - T G 之 培 養 基 中
以 細 胞 群 落 (c o l o n y )數 目 ,計 數 突 變 率
( 1 ) 突 變 率 ( 2 ) 細 胞 毒 性
離 心 後 去 除 化 學 物 質
計 算 細 胞 增 加 倍 數
R C N
1 2 ∼ 1 5 天
1 2 ∼ 1 5 天
接 種 於 含 T F T 之 培 養 基 中
6 ∼ 7 天
1 0天
再 加 T F T
1 0 天 3 ∼ 4 天