Moore M M, Amtower A, Doerr C L, Brock K H, Dearfield K L
Mutagenesis and Cellular Toxicology Branch, U. S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Environ Mol Mutagen. 1988;11(1):49-63. doi: 10.1002/em.2850110107.
A series of monomeric acrylate/methacrylate esters (methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate) as well as acrylic acid were examined for genotoxic activity in L5178Y mouse lymphoma cells without exogenous activation. All five compounds induced concentration-dependent increases in mutant frequency. Small-colony, trifluorothymidine-resistant mutants were primarily induced, which suggests that these compounds may act via a clastogenic mechanism. This prediction was confirmed by the finding that all five compounds produced gross chromosome aberrations in mouse lymphoma cells. The two acrylates were much more potent in their response than acrylic acid. Methyl acrylate (22 micrograms/ml, survival = 18%) induced 385 mutants/10(6) survivors (total mutant frequency less the spontaneous mutant frequency) and 45 chromosome aberrations/100 cells analyzed (total aberrations less the spontaneous background). Ethyl acrylate (37.5 micrograms/ml, survival = 15%) induced 683 mutants/10(6) survivors and 48 aberrations/50 cells analyzed. Acrylic acid (500 micrograms/ml, survival = 22%) induced 245 mutants/10(6) survivors and 37 aberrations/100 cells analyzed. The two methacrylates required higher concentrations to induce a positive response. Methyl methacrylate (2,799 micrograms/ml, survival = 11%) induced 230 mutants/10(6) survivors and 29 aberrations/200 cells analyzed. Ethyl methacrylate was extremely difficult to test because of a plateau in the dose response, over which the toxicity fluctuated from 2% to 37% survival. Positive responses (twice the spontaneous background) were only obtained at toxicity levels with less than approximately 20% survival. A concentration of 1,626 micrograms/ml (survival = 16%) induced 83 mutants/10(6) survivors and 11 aberrations/200 cells analyzed. The evidence suggests that the genotoxicity of these compounds is most likely due to a clastogenic mechanism.
在无外源性活化的情况下，对一系列单体丙烯酸酯/甲基丙烯酸酯（丙烯酸甲酯、丙烯酸乙酯、甲基丙烯酸甲酯和甲基丙烯酸乙酯）以及丙烯酸进行了L5178Y小鼠淋巴瘤细胞遗传毒性活性检测。所有这五种化合物均诱导突变频率呈浓度依赖性增加。主要诱导出小集落、抗三氟胸苷突变体，这表明这些化合物可能通过断裂机制起作用。这一预测通过以下发现得到证实：所有这五种化合物在小鼠淋巴瘤细胞中均产生了明显的染色体畸变。两种丙烯酸酯的反应比丙烯酸更有效。丙烯酸甲酯（22微克/毫升，存活率 = 18%）诱导出385个突变体/10⁶个存活细胞（总突变频率减去自发突变频率）以及45个染色体畸变/100个分析细胞（总畸变减去自发背景）。丙烯酸乙酯（37.5微克/毫升，存活率 = 15%）诱导出683个突变体/10⁶个存活细胞以及48个畸变/50个分析细胞。丙烯酸（500微克/毫升，存活率 = 22%）诱导出245个突变体/
