DNA ligand Hoechst-33342 enhances UV induced cytotoxicity in human glioma cell lines.
The effects of minor groove binding ligand bisbenzimidazole derivative Hoechst-33342 on the cellular response to UV damage have been studied in two human glioma cell lines BMG-1 and U-87 grown as monolayer cultures. Treatment induced cell death (macro-colony assay) and growth inhibition, potential lethal damage recovery, cytogenetic damage (micronuclei formation) and proliferation kinetics were studied as parameters for cellular response. Pre and post-irradiation treatment with Hoechst-33342 (1-20 microM) enhanced the UV-induced growth inhibition and cell death in a concentration dependent manner in both cell lines. At higher Hoechst-33342 concentrations (>5 microM), the cytotoxic effects of the combination (Hoechst-33342+UV) were highly synergistic and mainly mediated through apoptosis implying the possible interactions of lesions caused by both the agents. The enhanced cell death due to Hoechst-33342 was accompanied by a significant increase (2-3 folds at 5 microM) in UV-induced micronuclei formation in BMG-1 cells. Under these conditions, Hoechst-33342 also enhanced the UV-induced cell cycle delay, mainly due to S and G(2) blocks. The increase in UV-induced micronuclei formation observed after treatment with Hoechst-33342 indicates that the DNA bound Hoechst-33342 may interfere with the rejoining of DNA strand breaks. Since the treatment of cells with the replication inhibitor aphidicolin reduced the enhancement of UV induced cytotoxicity by Hoechst-33342, ongoing DNA replication appears to stimulate Hoechst-33342 and UV-induced cytotoxicity.
Singh
Shailja
S
Department of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Timarpur, Delhi 110054, India.
Dwarakanath
B S
BS
Mathew
T Lazar
TL
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001562:Benzimidazoles / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000378:metabolism*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D014466:Ultraviolet Rays
D001562:Benzimidazoles; D008024:Ligands; D004247:DNA; C017807:bisbenzimide ethoxide trihydrochloride