Induction of sister chromatid exchanges by the peroxisome proliferators 2,4-D, MCPA, and clofibrate in vivo and in vitro.
Induction of sister chromatid exchanges by the peroxisome proliferators 2,4-D, MCPA, and clofibrate in vivo and in vitro.
复制标题
过氧化物酶体增殖剂 2,4-D、MCPA 和安妥明在体内和体外诱导姐妹染色单体交换。
DOI：
10.1093/carcin/5.6.703
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发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
K. Linnainmaa
中科院分区：
文献类型：
--
作者：
K. Linnainmaa
已发现苯氧酸除草剂2，4-二氯苯氧乙酸（2，4-D）和4-氯-2-甲基苯氧乙酸（MCPA）以与降血脂药物氯贝丁酯相同的方式诱导啮齿动物肝细胞中过氧化物酶体的增殖。苯氧酸除草剂和氯贝特（乙基-α-对氯苯氧基异丁酸酯）都是疑似致癌物。本文报道了这些药物对染毒大鼠血淋巴细胞姐妹染色单体交换（SCE）的诱导作用（100 mg/kg与2，4-D和MCPA，200 mg/kg与氯贝丁酯，连续2周，每天一次灌胃给药），在暴露的中国仓鼠的骨髓细胞中（100 mg/kg，如上处理）和体外中国仓鼠卵巢（CHO）细胞（10（-5）、10（-4）和10（-3）M，1 h）。在体外实验中，除了商业除草剂制剂和氯贝丁酯的作用外，还研究了纯化的2，4-D和MCPA苯氧基酸的作用。与对照组相比，未观察到接触组大鼠血淋巴细胞SCE频率增加。2，4-D和氯贝丁酯组SCE无明显变化，而MCPA组SCE略有增加。SCE数量略微增加是所有处理CHO细胞培养物的特征，无论是否存在大鼠肝微粒体活化系统（S9混合物）。没有明确的剂量相关的影响，但是，可以看出与任何化合物，并没有差异，SCE诱导之间观察到的商业除草剂产品和纯化的苯氧基乙酸。目前的结果支持的数据表明，2，4-D，MCPA，和氯贝特不作为直接的DNA损伤剂。
Phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) have been found to induce proliferation of peroxisomes in the liver cells of rodents in the same manner as the hypolipidemic drug clofibrate. Both phenoxy acid herbicides and clofibrate (ethyl-alpha-p- chlorophenoxyisobutyrate ) are suspected carcinogens. The present study reports the effect of these agents on the induction of sister chromatid exchange (SCE) in the blood lymphocytes of exposed rats (100 mg/kg with 2,4-D and MCPA, 200 mg/kg with clofibrate for 2 weeks in one intragastric dose/day), in the bone marrow cells of exposed Chinese hamsters (100 mg/kg, treatments as above), and in Chinese hamster ovary (CHO) cells in vitro (10(-5), 10(-4), and 10(-3) M, for 1 h). In the experiments in vitro, the effects of purified 2,4-D and MCPA phenoxy acids were studied, in addition to those of the commercial herbicide formulations and clofibrate. No increase of SCE frequency was observed in the blood lymphocytes of the exposed rats in comparison with the controls. In the bone marrow cells of the exposed Chinese hamsters, a slight increase of SCE was found in the group treated with MCPA but not in the groups treated with 2,4-D or clofibrate. A slight increase in the number of SCEs was characteristic of all the treated CHO cell cultures, both with and without a rat liver microsomal activation system (S9 mix). No clear dose-related effects, however, could be discerned with any of the compounds, and no differences in the SCE induction were observed between the commercial herbicide products and the purified phenoxy acetic acids. The present results support the data which indicate that 2,4-D, MCPA, and clofibrate do not act as direct DNA-damaging agents.