Nitrogen mustard-mediated mutagenesis in human T-lymphocytes in vitro

Abstract

The cytotoxic and mutagenic effect of the bifunctional alkylating agent nitrogen mustard (HN₂) was examined. Primary human lymphocytes were exposed to graded doses of HN₂ in vitro and relative survival was determined. Mutation induction at the hypoxanthine-guanine phosphoribosyltransferase (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 μM. The mutant frequencies (MF) in exposed T-cell cultures were 10-fold (2 μM HN₂) to 32-fold (4 μM HN₂) higher than those of unexposed cultures (median values). Nitrogen mustard-mediated mutagenesis is discussed in terms of the current ideas about DNA damage and repair.