Molecular analysis of in vivo hprt mutations in human T lymphocytes. V. Effects of total body irradiation secondary to radioimmunoglobulin therapy (RIT)

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 (median 68.0 X 10(-6) for patients versus a median of 6.8 X 10(-6) for 115 controls). There was a good correlation of mutant frequency with initial activity of RIT (rlinear = 0.68, rquadratic = 0.76; P less than 0.05) although the correlation of mutant frequency with total activity after several rounds of treatment was poor (R = 0.18). 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 (r = 0.72) 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.