MacPhee D G
School of Microbiology, La Trobe University, Bundoora, Victoria 3083, Australia.
Mutat Res. 1998 Jun 18;402(1-2):29-39. doi: 10.1016/s0027-5107(97)00279-0.
Most attempts to identify potential antimutagens (and/or presumptive anticarcinogens) involve testing individual compounds or mixtures in tandem combinations with specific physical or chemical mutagens and measuring the sought-after reductions in mutation numbers in one or more experimental organisms. Relatively few investigators appear to have set out to identify antimutagens which are efficacious in reducing spontaneous mutation yields (possibly because of the poor mutation yields which tend to be available for downward manipulation in spontaneous mutation assays). The net effect is that we currently know very little about what may well prove to be one of the most interesting and exciting areas of antimutagenesis and anticarcinogenesis research in the future. This paper is primarily concerned with the main features of several interrelated (and often overlapping) pathways which are likely to be involved in the generation of newly-mutant sequences in cellular organisms in the absence of a deliberately-added mutagen. Attempts will be made to highlight some of the cellular processes which may have to be blocked in subtle (or perhaps even unsubtle) ways if we are to achieve our somewhat ambitious goal of discovering antimutagenic anticarcinogens which are both usable and useful in delaying the onset of primarily age-dependent mammalian cancers whose origins may well owe a great deal more to spontaneous mutations than they do to environmentally-provoked ones.
大多数鉴定潜在抗诱变剂（和/或推定抗癌剂）的尝试都涉及将单个化合物或混合物与特定的物理或化学诱变剂串联组合进行测试，并测量一种或多种实验生物体中突变数目的预期减少情况。相对较少的研究者似乎着手鉴定能有效降低自发突变率的抗诱变剂（可能是因为自发突变试验中可用于降低突变率的突变率较低）。其最终结果是，我们目前对未来抗诱变和抗癌研究中可能被证明是最有趣和最令人兴奋的领域之一的情况知之甚少。本文主要关注几个相互关联（且常常重叠）的途径的主要特征，这些途径可能参与了在没有故意添加诱变剂的情况下细胞生物体中新突变序列的产生。如果我们要实现发现既可用又有助于延迟主要由年龄引起的哺乳动物癌症发病的抗诱变抗癌剂这一颇具野心的目标，我们将尝试强调一些可能需要以微妙（甚至可能不那么微妙）的方式加以阻断的细胞过程，这类癌症的发生可能更多地归因于自发突变而非环境诱发突变。
