ANALYSIS OF POINT MUTATIONS IN THE HPRT GENE OF CANCER-PATIENTS TREATED WITH RADIOIMMUNOGLOBULIN THERAPY

The mutagenic impact of various environmental and therapeutic agents c an now be directly assayed in humans by the T-lymphocyte cloning assay . We have previously reported that following radioimmunoglobulin thera py, cancer patients exhibited increased mutant frequency at the hprt l ocus and an increased yield of large intergenic deletions compared to unexposed controls. Here we report the results of the analysis of 26 i ndependent hprt mutations in nine cancer patients who underwent radioi mmunoglobulin therapy. The majority of mutations (52%) had lost exon s equences from the mRNA. The remaining mutations were 20% small deletio ns and frameshifts and 28% base substitutions. The type of mutations o bserved were similar to those seen in unexposed controls. The site dis tribution of the mutations, however, indicates that some sequence cont exts may be more sensitive to radiation mutagenesis than others. (C) 1 995 Wiley-Liss, Inc.