Tarlo K S, Boehnke M, Chin B
Department of Environmental and Industrial Health, School of Public Health, University of Michigan, Ann Arbor 48109.
Mutat Res. 1988 Oct;206(2):239-46. doi: 10.1016/0165-1218(88)90167-x.
The effect of mixed mutagen exposures on the rate and type of induced mutants was studied in the L5178Y/TK+/-----TK-/- mouse lymphoma cell mutagenicity assay. In this assay, exposure to ethyl methanesulfonate (EMS) results in more mutants that form large colonies than small colonies. Exposure to methyl methanesulfonate (MMS) results in more mutants that form small colonies than large colonies. Other reports in the literature suggest that large colony TK-/- mutants appear to result from small-scale, perhaps single-gene mutations, and that small-colony TK-/- mutants appear to be associated with chromosomal mutations. Treating cells for 4 h with simple, 2-component mixtures containing 6.45 micrograms/ml MMS and either 261, 392, 560 or 712 micrograms/ml EMS resulted in synergism of mutants at each mixture level. The frequencies of total mutants were synergized 12, 20, 35 and 72%, respectively, in mixed exposures with graded doses of EMS, above the sums of the mixture components. Small colony mutants were synergized to a greater extent than large colony mutants. The frequencies of small colony mutants in mixed exposures were increased 31, 54, 73 and 123%, respectively, while the frequencies of large colony mutants were increased -7, -6, 11 and 39%. Statistical analyses provide strong evidence of synergism (within the limits of the assay) for total and small-colony mutants at all doses of EMS tested, and for large-colony mutants above 400 micrograms/ml EMS. Similar magnitudes of synergism resulted when other constant levels of MMS (4.30 or 8.60 micrograms/ml) were mixed with the same graded doses of EMS. The degree of synergism was dependent on EMS concentration but not on MMS concentration.
在L5178Y/TK+/-----TK-/-小鼠淋巴瘤细胞致突变性试验中，研究了混合诱变剂暴露对诱导突变体的速率和类型的影响。在该试验中，暴露于甲磺酸乙酯（EMS）会产生更多形成大菌落的突变体，而非小菌落突变体。暴露于甲磺酸甲酯（MMS）则会产生更多形成小菌落的突变体，而非大菌落突变体。文献中的其他报告表明，大菌落TK-/-突变体似乎源于小规模的，可能是单基因突变，而小菌落TK-/-突变体似乎与染色体突变有关。用含有6.45微克/毫升MMS和261、392、560或712微克/毫升EMS的简单二元混合物处理细胞4小时，在每个混合物水平上均导致突变体的协同作用。与分级剂量的EMS混合暴露时，总突变体的频率分别协同增加了12%、20%、35%和72%，高于混合物各成分的总和。小菌落突变体的协同作用程度大于大菌落突变体。混合暴露中小菌落突变体的频率分别增加了31%、54%、73%和123%，而大菌落突变体的频率分别增加了-7%、-6%、11%和39%。统计分析提供了有力证据，证明在所有测试的EMS剂量下，总突变体和小菌落突变体存在协同作用（在试验范围内），对于高于400微克/毫升EMS的大菌落突变体也存在协同作用。当其他恒定水平的MMS（4.30或8.60微克/毫升）与相同分级剂量的EMS混合时，产生了类似程度的协同作用。协同作用的程度取决于EMS浓度，而不取决于MMS浓度。
