NITROGEN MUSTARD-MEDIATED MUTAGENESIS IN HUMAN T-LYMPHOCYTES IN-VITRO

The cytotoxic and mutagenic effect of the bifunctional alkylating agen t nitrogen mustard (HN2) was examined. Primary human lymphocytes were exposed to graded doses of HN2 in vitro and relative survival was dete rmined. Mutation induction at the hypoxanthine-guanine phosphoribosylt ransferase (hprt) locus was measured by cloning the exposed T-cells in microtitre plates in the presence and absence of 6-thioguanine (TG). The IC50-value determined for 30 min exposure to HN2 was 1.34 mu M. Th e mutant frequencies (MF) in exposed T-cell cultures were 10-fold (2 m u M HN2) to 32-fold (4 mu M HN2) higher than those of unexposed cultur es (median values). Nitrogen mustard-mediated mutagenesis is discussed in terms of the current ideas about DNA damage and repair.