THE EFFECT OF T-LYMPHOCYTE CLONALITY ON THE CALCULATED HPRT MUTATION FREQUENCY OCCURRING IN-VIVO IN HUMANS

The frequency of 6-thioguanine resistant (TG(r)) 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 TG(r) mutant cells can distort the relationship between mutation event s and the resulting frequency of mutant cells. The T-cell receptor (TC R) gene rearrangement pattern of T-cell colonies can be used as an ind ependent measure of clonality. Analysis of T-cell 'clonality' in 413 w ild type and 1736 TG(r) 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 clonal ity (the calculated 'mutation frequency') was found only in nine sampl es all of which had mutant frequencies greater than 40 x 10(-6).