Molecular analysis of in vivo hprt mutations in human T lymphocytes: Pt. 5

The hprt (hypoxanthine guanine phosphoribosyltransferase) T cell cloning assay was used to detect in vivo mutations in T lymphocytes of individuals receiving radioimmunoglobulin therapy (RIT). A total of 28 patients receiving 131I and/or 90Y-labeled antiferritin antibodies was studied. Mutant frequencies for patients were clearly much higher than for historic non-treated controls. There was a good correlation of mutant frequency with initial activity of RIT although the correlation of mutant frequency with total activity after several rounds of treatment was poor. Molecular studies of the hprt mutants demonstrated that a much higher proportion of mutations occurring in RIT treated patients had gross structural alterations of the hprt gene (33%) than did mutations occurring in controls (15%). There was a good correlation of mutants with gross alterations and total RIT activity. T cell receptor gene studies demonstrated that most of the mutants (92%) represented independent in vivo mutations, which is similar to previous findings with background mutations in non-irradiated individuals. These studies demonstrate the usefulness of the hprt T cell cloning assay for studies of in vivo human somatic cell gene mutations resulting from ionizing radiation. (author)