Somatic mutation in biologic research1

In the last few years rapid progress has been made in several laboratories in the area of a possible etiologic role of somatic mutation in carcinogenesis and aging. Studies such as metabolic activation of an initial carcinogen to its active form, the genetic effects of tumor viruses, studies of DNA repair mechanisms, specific chromosomal patterns observed with banding techniques, and epidemiologic studies produce a strong probability of the involvement of mutational events in the initiation of malignancy. Similarly in aging, the observations that human fibroblast-like cells exhibited a finite lifespan in culture made it apparent that this could serve as one model to study cellular and molecular mechanisms of senescence in the absence of many of the complexities and variables found in the intact organism. Chromosomal mutations can be examined throughout the lifespan of these cells. In addition, specific locus mutations can be examined by somatic cell genetic techniques and various types of DNA repair can be studied. In this way a profile of genetic damage can be obtained sequentially with increasing chronologic age of these cells in an effort to estimate the role of somatic mutation as an etiological or modifying event of senescence in vitro.