Rodriguez H, Loechler E L
Department of Biology, Boston University, MA 02215.
Mutat Res. 1995 Jan;326(1):29-37. doi: 10.1016/0027-5107(95)00149-d.
(+)-anti-B[a]PDE-induced mutagenesis is being investigated, including in a supF gene of the E. coli plasmid pUB3. Based upon various findings a working hypothesis was proposed that the major adduct of (+)-anti-B[a]PDE (formed at N2-Gua) is able to induce different base substitution mutations (e.g., GC-->TA vs. GC-->AT vs. GC-->CG) depending upon its conformation in DNA, which can be influenced by various factors, such as DNA sequence context. Frameshift mutations are also significant and are analyzed herein. In virtually all cases one of three possibilities is observed: (1) some treatments change frameshift and base substitution mutation frequency (MF) in a quantitatively parallel fashion; (2) other treatments, which change frameshift MF, can change base substitution MF in a quantitatively reciprocal fashion; finally, (3) there are treatments that do not change frameshift MF, and also do not change base substitution MF. (Changes can be brought about by SOS induction, differing DNA sequence context, or heating adducted pUB3 prior to transformation. Why different kinds of changes result in (1) vs. (2) vs. (3) is discussed.) Thus, base substitution and frameshift mutagenesis pathways appear to be coupled in some way, which is most easily rationalized if both pathways are interrelated. The simplest mechanism to rationalize this coupling is that a single (+)-anti-B[a]PDE adduct in a single conformation can be bypassed via either a frameshift or a base substitution pathway. The surprising implication is that--although different conformations are likely to be required to induce different base substitution mutations (e.g., GC-->TA vs. GC-->AT; see above)--a single conformation can give rise to either a base substitution or a frameshift mutation. Frameshift and base substitution pathways must eventually diverge, and it is proposed that this is controlled by factors such as DNA sequence context.
正在研究（+）-反式苯并[a]芘二醇环氧化物（anti-B[a]PDE）诱导的诱变作用，包括在大肠杆菌质粒pUB3的supF基因中的诱变作用。基于各种研究结果，提出了一个工作假设，即（+）-anti-B[a]PDE的主要加合物（在N2-鸟嘌呤处形成）能够根据其在DNA中的构象诱导不同的碱基取代突变（例如，GC→TA与GC→AT与GC→CG），而这种构象会受到各种因素的影响，如DNA序列背景。移码突变也很显著，本文对此进行了分析。在几乎所有情况下，都会观察到三种可能性之一：（1）一些处理以定量平行的方式改变移码和碱基取代突变频率（MF）；（2）其他改变移码MF的处理，可以以定量相反的方式改变碱基取代MF；最后，（3）有些处理既不改变移码MF，也不改变碱基取代MF。（变化可能是由SOS诱导、不同的DNA序列背景或在转化前加热加合的pUB3引起的。文中讨论了为什么不同类型的变化会导致（1）与（2）与（3）的结果。）因此，碱基取代和移码诱变途径似乎以某种方式相互关联，如果这两种途径相互关联，那么这一点最容易得到合理的解释。解释这种关联的最简单机制是，单个构象的单个（+）-anti-B[a]PDE加合物可以通过移码或碱基取代途径被绕过。令人惊讶的是，尽管可能需要不同的构象来诱导不同的碱基取代突变（例如，GC→TA与GC→AT；见上文），但单个构象可以导致碱基取代或移码突变。移码和碱基取代途径最终必然会分开，并且有人提出这是由DNA序列背景等因素控制的。
