Effect of interferon-gamma on ACNU-induced DNA damage and cytotoxicity in human glioblastoma cells.
Interferons (IFNs) are a natural body defense with powerful effects on tumor growth, including gliomas. The direct effects of IFN-gamma on (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-induced deoxyribonucleic acid (DNA) damage and cytotoxicity were investigated in two human glioblastoma cell lines, A-172 and T98G, using a single cell microgel electrophoresis technique and a microculture tetrazolium assay. The results demonstrated a synergistic effect of IFN-gamma with ACNU on intracellular damage in both cell lines. 10 micrograms/ml ACNU induced a cell inhibition rate of 23.9% in A-172 cells, and almost no effect on T98G cells. 1000 U/ml IFN-gamma and 10 micrograms/ml ACNU caused a significant increase in cell inhibition, 51.2% for A-172 and 72.3% for T98G cells. DNA damage in individual A-172 and T98G cells exposed to ACNU was enhanced significantly by IFN-gamma (p < 0.001). The findings suggest a direct effect of IFN-gamma on ACNU-induced cell damage in human glioma, in addition to its effect on immunomodulation.
Zhang
W
W
Department of Neurosurgery, Gifu University School of Medicine.
Hara
A
A
Murakawa
T
T
Niikawa
S
S
Andoh
T
T
Sakai
N
N
Yamada
H
H
D001932:Brain Neoplasms / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004249:DNA Damage; D004357:Drug Synergism; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D015376:Nimustine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D015376:Nimustine; D007371:Interferon-gamma