The effect of T-lymphocyte 'clonality' on the calculated hprt mutation frequency occurring in vivo in humans.
The frequency of 6-thioguanine resistant (TGr) mutant T-lymphocytes arising in vivo in humans can be quantified with a cell cloning assay. However, the in vivo proliferation of T-lymphocytes that may include TGr mutant cells can distort the relationship between mutation events and the resulting frequency of mutant cells. The T-cell receptor (TCR) gene rearrangement pattern of T-cell colonies can be used as an independent measure of clonality. Analysis of T-cell 'clonality' in 413 wild type and 1736 TGr mutant isolates from 58 individuals shows that mutant clonality is a frequent occurrence (35/58 individuals = 60.3%). However, a major effect on the mutant frequency corrected for clonality (the calculated 'mutation frequency') was found only in nine samples all of which had mutant frequencies greater than 40 x 10(-6).
O'Neill
J P
JP
Vermont Cancer Center, University of Vermont, Burlington 05401.
Nicklas
J A
JA
Hunter
T C
TC
Batson
O B
OB
Allegretta
M
M
Falta
M T
MT
Branda
R F
RF
Albertini
R J
RJ
D001327:Autoimmune Diseases / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002999:Clone Cells; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006505:Hepatitis / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000235:genetics; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D013866:Thioguanine / Q000494:pharmacology
D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine