Goncharova R I, Zabrejko S, Kozachenko V I
Institute of Genetics and Cytology, Byelorussian Academy of Sciences, Minsk, U.S.S.R.
Mutat Res. 1988 Apr;204(4):703-9. doi: 10.1016/0165-1218(88)90076-6.
The mutagenic activity of dimethyl terephthalate (DMtP) was evaluated in the micronucleus test in mice. A clear clastogenic effect was obtained at all concentrations studied (0.2-1.0 mmole/kg body weight). The maximum number of micronuclei occurred 24 h after a single intraperitoneal (i.p.) injection. The time-course for the DMtP-induced micronuclei was in agreement with the available data on the rapid excretion of phthalates from the mammalian body. The dose-effect response was best described by a linear equation with a logarithmic component. The emergence of the latter term was related to the toxic effects of DMtP at higher concentrations on bone marrow erythropoietic function. A comparison of the effects induced by DMtP and by methyl nitrosourea indicated that DMtP cannot be considered a strong mutagenic compound. We have compared the sensitivity of the mouse micronucleus test and that of Drosophila dominant-lethal test by contrasting the effects obtained at similar exposure doses. This comparison leads to the conclusion that the micronucleus test is capable of responding to far lower phthalate concentrations than the Drosophila dominant-lethal mutation test. Our results testify to the ability of dimethyl terephthalate to cause genotoxic damages in vivo in both somatic and germinal cells of higher organisms. Thus, the chemical in question may be of potential genetic hazard to man.
在小鼠微核试验中评估了对苯二甲酸二甲酯（DMtP）的致突变活性。在所有研究浓度（0.2 - 1.0毫摩尔/千克体重）下均获得了明显的致断裂效应。单次腹腔注射后24小时出现微核数量最多的情况。DMtP诱导微核的时间进程与关于邻苯二甲酸盐从哺乳动物体内快速排泄的现有数据一致。剂量 - 效应反应最好用带有对数成分的线性方程来描述。后一项的出现与DMtP在较高浓度下对骨髓红细胞生成功能的毒性作用有关。对DMtP和甲基亚硝基脲诱导的效应进行比较表明，DMtP不能被视为一种强致突变化合物。我们通过对比在相似暴露剂量下获得的效应，比较了小鼠微核试验和果蝇显性致死试验的敏感性。这种比较得出的结论是，微核试验能够对远低于果蝇显性致死突变试验的邻苯二甲酸盐浓度做出反应。我们的结果证明了对苯二甲酸二甲酯能够在高等生物的体细胞和生殖细胞中在体内引起遗传毒性损伤。因此，所讨论的这种化学物质可能对人类具有潜在的遗传危害。
