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.
University of Vermont Genetic Toxicology Laboratory, 32 N. Prospect St., Burlington, VT 05401, USA.
R J
RJ
Albertini
J A
JA
Nicklas
T R
TR
Skopek
L
L
Recio
J P
JP
O'Neill
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