Cell proliferative activity estimated by histone H2B mRNA level correlates with cytogenetic damage induced by radiation in human glioblastoma cell lines.
We studied the relationship between proliferative activity and radiation-induced DNA damage in human malignant gliomas in vitro. Nine human glioblastoma established cell lines were gamma-irradiated (60Co) over a dose range of 0-10 Gy. H2B and H4 histone mRNA level was assessed with quantitative RT-PCR technique (TaqMan) and histone labeling index (HLI) with in situ hybridization to define proliferation rate, while cytochalasin-block micronucleus assay was performed to measure cytogenetic damage. Micronucleus frequency correlated with H2B mRNA level (Spearman's R up to 0.82 at 8 Gy), HLI, nuclear division index (NDI) and percentage of binucleated cells (%BNC). There was a high correlation between H2B mRNA level and NDI (R = 0.80) as well as %BNC and HLI (R = 0.72). Histone H2B and H4 mRNA level (not significant), HLI, NDI, and %BNC (significant) were higher in cell lines sensitive to DNA damage. Proliferative activity correlates with radiation-induced DNA damage in human glioma cell lines. Histone H2B mRNA level and HLI may be a useful molecular predictor of the tumour response to radiation treatment in gliomas of the same histological grade, however the risk of potentially more rapid tumour-cell repopulation must be considered. Presumed protective activity of histones against radiation-induced DNA damage was not confirmed at the transcript level.
Slowinski
Jerzy
J
Department of Neurosurgery and Neurotraumatology, Medical University of Silesia, Bytom, Poland. slowian@mp.pl
Mazurek
Urszula
U
Bierzynska-Macyszyn
Grazyna
G
Widel
Maria
M
Latocha
Malgorzata
M
Glogowska-Ligus
Joanna
J
Stomal
Monika
M
Mrowka
Ryszard
R
D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D006657:Histones / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015162:Micronucleus Tests; D009423:Nervous System Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D012333:RNA, Messenger / Q000378:metabolism* / Q000528:radiation effects; D011839:Radiation, Ionizing; D018709:Statistics, Nonparametric
D015415:Biomarkers; D006657:Histones; D012333:RNA, Messenger
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