Mutation

The earliest and still the most popular way to look at mutations is by cytogenetic means. This necessarily precludes the detection of mutational events smaller than a few million base pairs and also limits the target tissue to cells in metaphase, usually white blood cells. A noteworthy exception to this latter limitation is the original work of the late Howard Curtis (1963), who with coworkers examined mouse liver parenchymal cell metaphase plates after partial hepatectomy and found considerably higher numbers of cells with abnormal chromosomes in old, compared with young, animals (i.e., from about 10 percent of the cells in mice four to five months old to 75 percent in mice older than twelve months). Later, large structural changes in DNA were observed to increase with donor age in white blood cells of human individuals, from about 2–4 percent of the cells having chromosomal aberrations in young individuals to about six times higher in the elderly. The recent use of more advanced methods, such as chromosome painting, have confirmed the increase in cytogenetic damage with age in both human and mouse. In both human and mouse lymphocytes the increase in chromosome aberrations appeared to be exponential.