PMID- 30467642
OWN - NLM
STAT- MEDLINE
DCOM- 20200410
LR  - 20200410
IS  - 1432-2099 (Electronic)
IS  - 0301-634X (Linking)
VI  - 58
IP  - 1
DP  - 2019 Mar
TI  - Measurement of gamma-H2AX foci, miRNA-101, and gene expression as a means to quantify 
      radiation-absorbed dose in cancer patients who had undergone radiotherapy.
PG  - 69-80
LID - 10.1007/s00411-018-0767-0 [doi]
AB  - Radiological accidents and nuclear terrorism pose an increased threat to members 
      of the public who, following such an event, would need to be assessed for medical 
      care by fast triage. Assay methods such as chromosome aberrations (CA), 
      cytokinesis-block micronucleus (CBMN) and fluorescence in situ hybridization 
      (FISH) techniques have been well established for dose estimation and their 
      potential for handling more samples has also been proved with automation. 
      However, culturing of lymphocytes is an inevitable step, which limits the 
      potential of these markers for triage. In vitro analysis of gamma-H2AX (gamma-H2AX), 
      gene and microRNA (miRNA) markers do not require culturing of lymphocytes, and as 
      such have been suggested as attractive tools for triage. Despite studies 
      reporting in vitro dose-response curves, limited evidence is available evaluating 
      the suitability of these assays in real situations. In this study, we have 
      measured the absorbed dose using gamma-H2AX, gene (GADD45A, FDXR, and CDKN1A) and 
      miRNA-101 expression in blood samples of cancer patients (n = 20) who had 
      undergone partial-body radiotherapy and compared with the derived equivalent 
      whole-body doses (EWBD). The obtained results from all patients showed a 
      significant (p < 0.05) increase of gamma-H2AX foci in post-irradiated as compared to 
      pre-irradiated samples. Moreover, estimated doses using gamma-H2AX foci showed a 
      correlation with the derived EWBD (r(2) = 0.60, p = 0.0003) and was also shown to 
      be dependent on the irradiated body volume. Consistent with gamma-H2AX foci 
      frequency, an increase in fold change expression of genes and miRNA-101 was 
      observed. However, the estimated dose significantly varied among the subjects and 
      showed poor correlation (r(2) = 0.09, 0.04, 0.01 and 0.03 for GADD45A, FDXR, 
      CDKN1A and miRNA-101, respectively) with EWBD. The overall results suggest that 
      the established in vitro gamma-H2AX assay is suitable for the detection of radiation 
      exposure and can also provide an estimate of the dose in in vivo irradiated 
      samples. The genes and miRNA-101 markers showed increased expression; 
      nevertheless, there is a need for further improvements to measure doses 
      accurately using these markers.
FAU - Raavi, Venkateswarlu
AU  - Raavi V
AD  - Department of Human Genetics, Sri Ramachandra Medical College and Research 
      Institute (Deemed to be University), Porur, Chennai, 600 116, India.
FAU - Surendran, J
AU  - Surendran J
AD  - Department of Radiation Oncology, Kamakshi Memorial Hospital, Pallikaranai, 
      Chennai, 600 100, India.
FAU - Karthik, K
AU  - Karthik K
AD  - Department of Human Genetics, Sri Ramachandra Medical College and Research 
      Institute (Deemed to be University), Porur, Chennai, 600 116, India.
FAU - Paul, Solomon F D
AU  - Paul SFD
AD  - Department of Human Genetics, Sri Ramachandra Medical College and Research 
      Institute (Deemed to be University), Porur, Chennai, 600 116, India.
FAU - Thayalan, K
AU  - Thayalan K
AD  - Department of Radiation Oncology, Kamakshi Memorial Hospital, Pallikaranai, 
      Chennai, 600 100, India.
FAU - Arunakaran, J
AU  - Arunakaran J
AD  - Department of Endocrinology, Dr. ALM PGIBMS, University of Madras, Taramani, 
      Chennai, 600 113, India.
FAU - Venkatachalam, Perumal
AU  - Venkatachalam P
AUID- ORCID: 0000-0003-2152-2003
AD  - Department of Human Genetics, Sri Ramachandra Medical College and Research 
      Institute (Deemed to be University), Porur, Chennai, 600 116, India. 
      venkip@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - Germany
TA  - Radiat Environ Biophys
JT  - Radiation and environmental biophysics
JID - 0415677
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (GADD45A protein, human)
RN  - 0 (H2AX protein, human)
RN  - 0 (Histones)
RN  - 0 (MIRN101 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Cell Cycle Proteins/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics
MH  - Dose-Response Relationship, Radiation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*radiation effects
MH  - Histones/*blood
MH  - Humans
MH  - Lymphocytes/metabolism/radiation effects
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Neoplasms/blood/genetics/*radiotherapy
MH  - *Radiation Dosage
OTO - NOTNLM
OT  - Biomarkers
OT  - Gene expression
OT  - MicroRNA
OT  - Radiotherapy
OT  - gamma-H2AX foci
EDAT- 2018/11/24 06:00
MHDA- 2020/04/11 06:00
CRDT- 2018/11/24 06:00
PHST- 2018/05/29 00:00 [received]
PHST- 2018/11/12 00:00 [accepted]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2020/04/11 06:00 [medline]
PHST- 2018/11/24 06:00 [entrez]
AID - 10.1007/s00411-018-0767-0 [pii]
AID - 10.1007/s00411-018-0767-0 [doi]
PST - ppublish
SO  - Radiat Environ Biophys. 2019 Mar;58(1):69-80. doi: 10.1007/s00411-018-0767-0. 
      Epub 2018 Nov 22.