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.
Nicklas
J A
JA
Vermont Regional Cancer Center, Burlington.
Falta
M T
MT
Hunter
T C
TC
O'Neill
J P
JP
Jacobson-Kram
D
D
Williams
J R
JR
Albertini
R J
RJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000532:radiotherapy*; D015321:Gene Rearrangement; D005796:Genes / Q000528:radiation effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D008875:Middle Aged; D009154:Mutation; D013601:T-Lymphocytes / Q000201:enzymology / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D007041:Hypoxanthine Phosphoribosyltransferase