Albertini R J, O'Neill J P, Nicklas J A, Heintz N H, Kelleher P C
Nature. 1985;316(6026):369-71. doi: 10.1038/316369a0.
Investigations into the extent and significance of somatic gene mutations occurring in vivo in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of in vivo-derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of in vivo somatic mutation. We and others have since described methods for the isolation and study of these unusual cells. The thioguanine-resistant T cell stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal hprt Lesch-Nyhan germinal mutation. We now report that in vivo-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of hprt structural alterations, as determined by Southern blot analysis. This finding demonstrates unequivocally that these cells are genetic mutants and validates their use for fundamental and applied mutational studies in humans.
由于缺乏明确界定体内衍生变异细胞突变起源的方法，对人类体内发生的体细胞基因突变的程度和意义的研究受到了阻碍。几年前，我们提出，存在于人类外周血中低频的6-硫鸟嘌呤抗性T淋巴细胞可能是体内体细胞突变的有用标志物。从那以后，我们和其他人描述了分离和研究这些异常细胞的方法。硫鸟嘌呤抗性T细胞稳定地缺乏次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）活性，这表明它们在正常个体中是X染色体hprt莱施-奈恩生殖系突变个体细胞的体细胞等效物。我们现在报告，通过Southern印迹分析确定，来自单个正常个体的体内衍生硫鸟嘌呤抗性T细胞集落显示出多种hprt结构改变。这一发现明确证明这些细胞是遗传突变体，并验证了它们在人类基础和应用突变研究中的用途。
