Phillips B J, Anderson D, Gangolli S D
Environ Health Perspect. 1986 Mar;65:263-6. doi: 10.1289/ehp.8665263.
Mono(2-ethylhexyl) phthalate (MEHP) induced chromosome aberrations in cells of two culture lines, one derived from Chinese hamster ovary cells (CHO) and the other from rat liver cells (RL4). In CHO cells, the clastogenicity of MEHP was unaffected by the presence of an exogenous metabolic activation system (S-9 mix). 2-Ethylhexanol, o-phthalic acid, and phthalic anhydride were without effect. Cytochemical methods and assays for carnitine acetyltransferase and KCN-insensitive palmitoyl CoA oxidation were employed to determine whether chromosome damage was associated with peroxisome proliferation. No evidence of an increase in peroxisome numbers or of induction of marker enzymes was found in CHO cells treated with MEHP for up to 72 hr. Clofibric acid and BR931 were also ineffective. Observations on changes in CHO cell structure and permeability, and on the haemolytic effects of phthalate monoesters, suggest that the cytotoxicity of MEHP may be due primarily to its action on cell membranes. Since chromosome damage was observed only at cytotoxic concentrations, it is suggested that damage to lysosomal membranes and the release of endonucleases may be responsible for the observed clastogenicity of MEHP in vitro.
邻苯二甲酸单（2-乙基己基）酯（MEHP）在两种培养细胞系中诱发了染色体畸变，一种源自中国仓鼠卵巢细胞（CHO），另一种源自大鼠肝细胞（RL4）。在CHO细胞中，MEHP的致断裂性不受外源性代谢激活系统（S-9混合物）存在的影响。2-乙基己醇、邻苯二甲酸和邻苯二甲酸酐无此作用。采用细胞化学方法以及肉碱乙酰转移酶和对KCN不敏感的棕榈酰辅酶A氧化的检测方法，以确定染色体损伤是否与过氧化物酶体增殖有关。在用MEHP处理长达72小时的CHO细胞中，未发现过氧化物酶体数量增加或标记酶诱导的证据。氯贝酸和BR931也无效。对CHO细胞结构和通透性变化以及邻苯二甲酸单酯溶血作用的观察表明，MEHP的细胞毒性可能主要归因于其对细胞膜的作用。由于仅在细胞毒性浓度下观察到染色体损伤，因此有人提出，溶酶体膜的损伤和核酸内切酶的释放可能是体外观察到的MEHP致断裂性的原因。
