Ferguson L R, von Borstel R C
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Mutat Res. 1992 Jan;265(1):103-48. doi: 10.1016/0027-5107(92)90042-z.
A range of physical and chemical agents induce the mitochondrial 'petite' mutation in the yeast Saccharomyces cerevisiae. DNA intercalating agents as well as chemicals which can interfere with DNA synthesis induce this mutation, but only in growing cells. Many chemical or physical agents that produce a DNA lesion which is not simply reversed can induce various levels of the petite mutation, and may be more effective in non-growing cells. A limited number of chemicals act like ethidium bromide, inducing a high frequency of petites which is partially reversible with increasing concentration or time. The ability of a specific compound to be transported into mitochondria or its affinity for AT base pairs in DNA may determine whether it acts primarily as a nuclear or mitochondrial mutagen. In mammalian cells, some neoplastic changes occur at the mitochondrial level. Analogies between yeast and mammalian mitochondria suggest that agents which increase petite mutagenesis in yeast may have some carcinogenic potential. Although some types of petite inducer may have potential as antitumour drugs, those which are very effective antimitochondrial agents appear to be too toxic for therapeutic use. A process comparable to early stages in petite mutagensis occurs in human degenerative diseases and it seems possible that a consequence of exposure to petite mutagens could be an increase in the rate of degenerative diseases or of the aging process.
一系列物理和化学因子可诱导酿酒酵母中的线粒体“小菌落”突变。DNA嵌入剂以及能够干扰DNA合成的化学物质均可诱导此突变，但仅在生长细胞中起作用。许多产生并非简单逆转的DNA损伤的化学或物理因子可诱导不同水平的小菌落突变，并且在非生长细胞中可能更有效。有限数量的化学物质的作用类似于溴化乙锭，可诱导高频率的小菌落突变，随着浓度增加或时间延长，这种突变部分可逆。特定化合物转运到线粒体中的能力或其对DNA中AT碱基对的亲和力可能决定其主要作为核诱变剂还是线粒体诱变剂起作用。在哺乳动物细胞中，一些肿瘤性变化发生在线粒体水平。酵母和哺乳动物线粒体之间的相似性表明，在酵母中增加小菌落诱变的因子可能具有一定的致癌潜力。尽管某些类型的小菌落诱导剂可能具有作为抗肿瘤药物的潜力，但那些非常有效的抗线粒体药物似乎因毒性太大而无法用于治疗。在人类退行性疾病中会发生与小菌落诱变早期阶段类似的过程，接触小菌落诱变剂的一个后果可能是退行性疾病发生率或衰老过程加快。
