Induction of 8-azaguanine resistance and sister chromatid exchange in human lymphocytes exposed to mitomycin C and X rays in vitro

Indirect evidence implies that 8-azaguanine-resistant (AGsup(r)) lymphocytes in human peripheral blood are mutants associated with the loss of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus on the active X chromosome, the mutation frequency increasing linearly with age. AGsup(r) variants are readily induced in lymphocytes exposed to mitomycin C in vitro, their incidence correlating with induced sister chromatid exchanges (SCEs). Although SCE events and the development of an AGsup(r) phenotype may reflect a common type of DNA damage, mitomycin C-induced AGsup(r) variants are not mutants but are suggested to be cells having a transcriptional block at the HPRT locus. AGsup(r) variants are also readily induced by X rays in vitro, their incidence correlates closely with the incidence of aberrations induced in the X chromosome and they are considered to have a mutational origin. (author)