title: Cell proliferative activity estimated by histone H2B mRNA level correlates with cytogenetic damage induced by radiation in human glioblastoma cell lines.
abstract: 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.
authors.affiliation: Department of Neurosurgery and Neurotraumatology, Medical University of Silesia, Bytom, Poland. slowian@mp.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Slowinski
authors.forename: Urszula
authors.initials: U
authors.lastname: Mazurek
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bierzynska-Macyszyn
authors.forename: Maria
authors.initials: M
authors.lastname: Widel
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Latocha
authors.forename: Joanna
authors.initials: J
authors.lastname: Glogowska-Ligus
authors.forename: Monika
authors.initials: M
authors.lastname: Stomal
authors.forename: Ryszard
authors.initials: R
authors.lastname: Mrowka
mesh_terms: 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
chemical_list: D015415:Biomarkers; D006657:Histones; D012333:RNA, Messenger
references.citation: Neoplasma. 1999;46(1):40-9
references.pmid: 10355533
references.citation: Radiother Oncol. 1995 Aug;36(2):128-32
references.pmid: 7501810
references.citation: Mutat Res. 2003 Jan 10;534(1-2):65-75
references.pmid: 12504755
references.citation: Genome Res. 1996 Oct;6(10):986-94
references.pmid: 8908518
references.citation: Int J Radiat Oncol Biol Phys. 1992;23(1):55-62
references.pmid: 1315313
references.citation: Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Apr;49(4):611-20
references.pmid: 3485603
references.citation: Cancer. 2000 Oct 1;89(7):1526-31
references.pmid: 11013367
references.citation: Radiat Res. 1991 Dec;128(3):293-300
references.pmid: 1961926
references.citation: Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Feb;49(2):357-80
references.pmid: 3510997
references.citation: Radiat Res. 1997 Aug;148(2):188-92
references.pmid: 9254739
references.citation: Br J Cancer. 1996 Oct;74(8):1223-6
references.pmid: 8883408
references.citation: Int J Radiat Biol. 1994 Jan;65(1):103-8
references.pmid: 7905902
references.citation: Int J Radiat Oncol Biol Phys. 1990 Dec;19(6):1397-403
references.pmid: 2262364
references.citation: Neoplasma. 1995;42(5):243-8
references.pmid: 8552203
references.citation: Int J Radiat Oncol Biol Phys. 1992;23(2):339-43
references.pmid: 1316889
references.citation: Histopathology. 1998 Jan;32(1):43-50
references.pmid: 9522215
references.citation: Genome Res. 1996 Oct;6(10):995-1001
references.pmid: 8908519
references.citation: Strahlenther Onkol. 1992 Oct;168(10):603-9
references.pmid: 1440232
references.citation: Int J Radiat Oncol Biol Phys. 1985 Sep;11(9):1699-707
references.pmid: 4030437
references.citation: Folia Histochem Cytobiol. 2002;40(4):335-9
references.pmid: 12502183
references.citation: Mutat Res. 1996 Jun 10;352(1-2):123-34
references.pmid: 8676901
references.citation: Mutat Res. 1998 Sep 25;418(1):49-57
references.pmid: 9748498
references.citation: Strahlenther Onkol. 2002 Sep;178(9):491-6
references.pmid: 12426835
references.citation: J Pathol. 1994 Dec;174(4):275-82
references.pmid: 7884589
references.citation: Neoplasma. 1997;44(2):109-16
references.pmid: 9201290
references.citation: Cell Differ. 1983 Jan;12(1):47-55
references.pmid: 6825177
references.citation: Radiat Res. 1991 Apr;126(1):58-64
references.pmid: 2020739
references.citation: Acta Oncol. 2001;40(8):989-94
references.pmid: 11845965
references.citation: Int J Radiat Biol. 1992 Oct;62(4):389-96
references.pmid: 1357051
references.citation: Science. 1974 May 24;184(4139):868-71
references.pmid: 4825889
references.citation: Radiother Oncol. 1990 Mar;17(3):177-90
references.pmid: 2181561
references.citation: Int J Radiat Biol. 1994 Nov;66(5):523-9
references.pmid: 7983440
references.citation: Eur J Cancer. 1993;29A(10):1454-61
references.pmid: 8398275
references.citation: Radiat Res. 1997 Jan;147(1):29-34
references.pmid: 8989366
references.citation: Int J Radiat Biol. 2001 May;77(5):631-6
references.pmid: 11382342
references.citation: Anal Biochem. 1987 Apr;162(1):156-9
references.pmid: 2440339
references.citation: J Radiat Res. 1994 Mar;35(1):11-5
references.pmid: 8057266
references.citation: Radiology. 1977 Oct;125(1):231-4
references.pmid: 197567
references.citation: Mutat Res. 2000 Nov 20;455(1-2):81-95
references.pmid: 11113469