Albertini R J, Nicklas J A, Skopek T R, Recio L, O'Neill J P
University of Vermont Genetic Toxicology Laboratory, 32 N. Prospect St., Burlington, VT 05401, USA.
Mutat Res. 1998 May 25;400(1-2):381-9. doi: 10.1016/s0027-5107(98)00063-3.
Mutations arising in vivo in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene of T-lymphocytes provide a measure of mutation induction in human somatic cells. Studies of measured background HPRT mutant frequency (MF) values show wide inter-individual variation. At the extremes are individuals with 'outlier' MF values, i.e., non-exposed individuals with MF>100x10-6 [Robinson et al., Mutation Res. 313 (1994) 227-247.]. The elevated HPRT MF in one well-studied outlier is due to the in vivo expansion of mutant cells possessing an identical T-cell receptor (TCR) gene rearrangement pattern. We report here that this in vivo expanding TCR clone shows multiple different HPRT mutations and thus possesses a mutator phenotype. Other individuals with T-cell mutator phenotypes have been found, suggesting that this phenomenon may contribute to the extremes of variation in HPRT MFs in the human population.
T淋巴细胞次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）基因在体内发生的突变可用于衡量人类体细胞中的突变诱导情况。对测得的背景HPRT突变频率（MF）值的研究表明，个体间存在广泛差异。处于极端情况的是具有“异常值”MF值的个体，即MF>100×10⁻⁶的未接触个体[罗宾逊等人，《突变研究》313（1994）227 - 247]。在一个经过充分研究的异常个体中，HPRT MF升高是由于具有相同T细胞受体（TCR）基因重排模式的突变细胞在体内扩增所致。我们在此报告，这种在体内扩增的TCR克隆显示出多种不同的HPRT突变，因此具有突变表型。还发现了其他具有T细胞突变表型的个体，这表明这种现象可能导致了人群中HPRT MF变化的极端情况。
