Somatic gene mutations in vivo as indicated by the 6-thioguanine-resistant T-lymphocytes in human blood

Abstract

The clonal and the autoradiographic assays for 6-thioguanine-resistant (TG r) T-lymphocytes (T-Lys) in human blood are reviewed. Studies of TG r colonies recovered from clonal assays show that the mutant T-Lys (i) are either helper (T4) or suppressor (T8) cells, (ii) poses stable TG r phenotype, (iii) are deficient in hypoxanthine guanine phosphoribosyltransferase (HPRT), and (iv) have structural alterations in the hprt gene. TG r T-Ly mutant frequencies (Mfs) determined by clonal assays are of the order of 10 −6−10 −5 for normal adults. Autoradiographically determined variant frequencies (Vfs) are also in this range for normal adults when lymphocytes are cryopreserved before study to remove ‘phenocopies’. Cancer exposed to potentially mutagenic treatments have elevated TG r T-Ly Vfs. Comparative clonal and autoradiographic assays of the same blood samples give generally similar results when allowances are made for potential sources of error in each assay. The TG r T-Ly system is presented for human specific-locus mutagenicity monitoring.