Mutation Induction by ¹²⁵iodoacetylproflavine, a DNA-intercalating Agent, in Human Cells

Summary

Survival and the induction of mutations at the hprt and tk loci were measured in TK6 human lymphoblastoid cells following treatment with the DNA-intercalating agent ¹²⁵iodoacetylproflavine (¹²⁵IAP). ¹²⁵IAP was readily taken up into the cells, was localized to the nucleus, and was released rapidly following resuspension of the cells in fresh medium. Treatment with ¹²⁵IAP for 24 h yielded a D₀ of 110 decays/cell and an induced mutant fraction of 0·13 × 10⁻⁶ per decay at the hprt locus and 0·4 × 10⁻⁶ per decay at the tk locus. Molecular analyses of ¹²⁵IAP-induced hprt mutants by Southern blot revealed a high proportion of large-scale changes at this locus. When these results are compared with those observed with ¹²⁵IdUrd, ¹²⁵IAP shows a reduced effectiveness per decay, related perhaps to the non-covalent nature of intercalator binding, resulting in reduced energy deposition in the DNA.