Tayama S, Kamiya N, Nakagawa Y
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Mutat Res. 1989 May;223(1):23-33. doi: 10.1016/0165-1218(89)90059-1.
The effects of microsomal activation and/or deactivation on the induction of chromosomal aberrations and sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary cells (CHO-K1 cells) by o-phenylphenol (OPP) were studied, and concurrently the metabolites were determined. After a 3-h incubation in the presence of 15% S9 mix (45 microliters/ml of S9), OPP (25-150 micrograms/ml) dose-independent SCEs and chromosomal aberrations were induced, while the amount of phenylhydroquinone (PHQ) metabolite produced from OPP did not increase linearly in the higher doses. The maximum induction of chromosomal aberrations was 18% at the 150 micrograms/ml dose, and of SCEs 13.8/cell at 75 micrograms/ml. The corresponding control values were 3% and 5.8/cell. The lowest dose required to induce SCEs in the presence of S9 mix was 25 micrograms/ml. Changing the percent of S9 mix (0-50%) while holding the OPP dose constant (100 micrograms/ml) produced a correlation between SCEs and the production of PHQ. PHQ caused cytogenetic effects both with and without S9 mix, however, in the absence of S9 mix it was more lethal and was oxidized to phenylbenzoquinone (PBQ). These results suggest that the enhanced cytogenetic effects of OPP by the addition of S9 mix correlated with the amount of PHQ produced or with the further oxides of PHQ such as phenylsemiquinone and/or PBQ which are capable of being produced from PHQ spontaneously or by the mixed-function oxidase system.
研究了微粒体激活和/或失活对邻苯基苯酚（OPP）诱导培养的中国仓鼠卵巢细胞（CHO-K1细胞）染色体畸变和姐妹染色单体交换（SCE）的影响，并同时测定了代谢产物。在含有15% S9混合液（45微升/毫升S9）的条件下孵育3小时后，OPP（25 - 150微克/毫升）诱导了剂量无关的SCE和染色体畸变，而OPP产生的对苯二酚（PHQ）代谢产物的量在较高剂量下并未呈线性增加。在150微克/毫升剂量下，染色体畸变的最大诱导率为18%，在75微克/毫升剂量下，SCE的最大诱导率为13.8/细胞。相应的对照值分别为3%和5.8/细胞。在存在S9混合液的情况下诱导SCE所需的最低剂量为25微克/毫升。在保持OPP剂量恒定（100微克/毫升）的同时改变S9混合液的百分比（0 - 50%），SCE与PHQ的产生之间呈现相关性。无论有无S9混合液，PHQ均会引起细胞遗传学效应，然而，在没有S9混合液的情况下，它更具致死性，并被氧化为苯醌（PBQ）。这些结果表明，添加S9混合液后OPP细胞遗传学效应的增强与PHQ的产生量或PHQ的进一步氧化产物如苯半醌和/或PBQ相关，这些氧化产物能够由PHQ自发产生或通过混合功能氧化酶系统产生。
