Oller A R, Rastogi P, Morgenthaler S, Thilly W G
Toxicology Group, Massachusetts Institute of Technology, Cambridge 02139.
Mutat Res. 1989 Jun;216(3):149-61. doi: 10.1016/0165-1161(89)90001-0.
Long term-low dose mutation assays offer a means to study the genetic effects of environmental mutagens at concentrations relevant to human exposure. These assays involve continuous induction of mutants, serial dilution of cultures and sampling to determine the mutant fraction as a function of time and mutagen concentration. An arithmetic model for the expected variance among identically treated cultures is presented. This model provides means to calculate a predicted variance of the mutant fractions and mutation rates in typical long term-low dose experiments. We have calculated the expected variances of the mutant fraction with this model and compared them to the observed variances among 4 independent experiments in which human lymphoblastoid cells were treated for 5, 10, 15 and 20 days with a non-toxic concentration of the mutagen 4-aminobiphenyl. Mutations at the HPRT locus were measured by determining the 6-thioguanine-resistant mutant fraction. The expected and observed variances of the mutant fractions are in close agreement. This model is adequate to predict the variance of the mutant fraction and should be useful in experimental design and objective evaluation of long term-low dose mutation assays.
长期低剂量突变试验提供了一种手段，用于研究与人类接触相关浓度下环境诱变剂的遗传效应。这些试验包括持续诱导突变体、对培养物进行连续稀释并取样，以确定作为时间和诱变剂浓度函数的突变体比例。本文提出了一个关于相同处理培养物预期方差的算术模型。该模型提供了计算典型长期低剂量实验中突变体比例和突变率预测方差的方法。我们用这个模型计算了突变体比例的预期方差，并将其与4个独立实验中观察到的方差进行了比较。在这些实验中，人类淋巴母细胞用无毒浓度的诱变剂4-氨基联苯处理5、10、15和20天。通过测定6-硫鸟嘌呤抗性突变体比例来检测次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）位点的突变。突变体比例的预期方差和观察到的方差非常吻合。该模型足以预测突变体比例的方差，并且应该对长期低剂量突变试验的实验设计和客观评估有用。
