Genetic instability in human T-lymphocytes.
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.
Albertini
R J
RJ
University of Vermont Genetic Toxicology Laboratory, 32 N. Prospect St., Burlington, VT 05401, USA.
Nicklas
J A
JA
Skopek
T R
TR
Recio
L
L
O'Neill
J P
JP
D000328:Adult; D002999:Clone Cells; D004252:DNA Mutational Analysis; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016296:Mutagenesis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D007041:Hypoxanthine Phosphoribosyltransferase