Mutation induction by 125iodoacetylproflavine, a DNA-intercalating agent, in human cells.
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 x 10(-6) per decay at the hprt locus and 0.4 x 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.
Whaley
J M
JM
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Kassis
A I
AI
Kinsey
B M
BM
Adelstein
S J
SJ
Little
J B
JB
D000166:Acridines / Q000493:pharmacokinetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D009154:Mutation; D011370:Proflavine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D013937:Thymidine Kinase / Q000235:genetics
D000166:Acridines; D007364:Intercalating Agents; D007457:Iodine Radioisotopes; C059684:3-acetamido-5-iodoproflavine; D011370:Proflavine; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase