Naito M, DiGiovanni J
University of Texas System Cancer Center, Science Park-Research Division, Smithville 78957.
Carcinog Compr Surv. 1989;11:187-212.
Inbred mouse strains that differing widely in their susceptibility to multistage skin carcinogenesis provide useful models for studying the genetic factors involved and advancing our understanding of the biochemical and molecular events associated with this process. The process of skin tumor initiation appears to be somewhat similar in various strains of mice, and most data in the literature suggest that differences in response to skin tumor promoters are a major determinant in controlling susceptibility to multistage skin carcinogenesis. A model system has been developed for examining the genetics of susceptibility to skin tumor promotion. The susceptibility to phorbol ester skin tumor promotion in crosses between DBA/2 and C57BL/6 mice is inherited as an incomplete dominant trait, and neither X-chromosome nor cytoplasmic genetic determinants appear to play a major role in determining susceptibility in these two inbred strains. In addition, two or more genetic loci contribute to the higher sensitivity of DBA/2 mice than C57BL/6 mice to TPA-induced skin tumor promotion. Further studies to characterize these genes will contribute greatly to our understanding of the mechanisms of phorbol ester skin tumor promotion. In addition, much work should now be directed at understanding the cellular, biochemical, and molecular mechanisms for differential responsiveness not only to phorbol esters but also to other classes of tumor promoters.
在对多阶段皮肤癌发生的易感性上差异很大的近交系小鼠品系，为研究其中涉及的遗传因素以及增进我们对与该过程相关的生化和分子事件的理解提供了有用的模型。皮肤肿瘤起始过程在各种小鼠品系中似乎有些相似，并且文献中的大多数数据表明，对皮肤肿瘤促进剂反应的差异是控制对多阶段皮肤癌发生易感性的主要决定因素。已经开发出一个模型系统来研究对皮肤肿瘤促进的易感性遗传学。DBA/2和C57BL/6小鼠杂交后代对佛波酯皮肤肿瘤促进的易感性作为一种不完全显性性状遗传，并且在这两个近交系中，X染色体和细胞质遗传决定因素似乎在决定易感性方面都不发挥主要作用。此外，两个或更多个基因位点导致DBA/2小鼠比C57BL/6小鼠对TPA诱导的皮肤肿瘤促进具有更高的敏感性。进一步表征这些基因的研究将极大地有助于我们理解佛波酯皮肤肿瘤促进的机制。此外，现在许多工作应致力于理解不仅对佛波酯而且对其他类肿瘤促进剂产生差异反应的细胞、生化和分子机制。
