Document Detail


Biodosimetry for high dose accidental exposures by drug induced premature chromosome condensation (PCC) assay.
MedLine Citation:
PMID:  20338261     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The conventional dicentric assay does not provide an accurate dose estimate in the case of accidental exposure to ionizing radiation above 6 Gy due to mitotic delay and poor mitotic index. The present study aims to establish a simple and rapid dose assessment technique based on scoring of rings and fragments in PCC spreads of stimulated lymphocytes. Human peripheral blood lymphocytes were gamma irradiated to different doses (6.2-24.5 Gy), cultured for two days with PHA and were forced to condense prematurely using 500 nM Okadaic acid (OA). The chromosome spreads were prepared, stained with Giemsa and observed under a microscope. The PCC index, PCC rings, and PCC fragments were scored for each dose point to arrive at the dose effect curve for various end points such as induction of rings and fragments and dicentrics. The PCC index varied from 12-18% up to 18 Gy and thereafter dropped to 6-8% at higher doses. The dose dependent increase in rings and fragments was found to be linear with a slope of 0.054+/-0.001 Gy(-1) for rings and 0.45+/-0.03 Gy(-1) for PCC fragments. An experiment was carried out to simulate partial-body exposure by mixing 10 Gy in vitro irradiated blood with un-irradiated blood in different proportions. The ratio of frequency of damaged cells among the total number of cells analyzed was found to be a good index of partial-body exposure. The culture duration was extended to 72 h to overcome the cell cycle delay induced by high doses of radiation. The conventional dicentrics rings and fragments also showed a dose response at high doses. The response can be best fitted to a linear model with a slope of 0.28+/-0.0007 Gy(-1) for the induction of dicentrics. However, long culture duration, technical skill and time required to analyse multi-aberrant cells makes the dicentric assay less suitable for high dose exposures requiring a rapid dose estimate. The PCC assay can be performed in 50 h with biodosimetric information about the irradiated fraction in cases of acute radiation exposures. The automated finding of PCC spreads significantly increased the speed of scoring PCC fragments.
Authors:
Sreedevi Balakrishnan; Kapil Shirsath; Nagesh Bhat; Kshiti Anjaria
Publication Detail:
Type:  Journal Article     Date:  2010-03-23
Journal Detail:
Title:  Mutation research     Volume:  699     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  11-6     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Affiliation:
Radiological Physics & Advisory Division, Bhabha Atomic Research Centre Trombay, Mumbai, India. bsdevi@barc.gov.in
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MeSH Terms
Descriptor/Qualifier:
Adult
Cells, Cultured
Chromosome Aberrations* / radiation effects
Chromosomes, Human / radiation effects*
Dose-Response Relationship, Radiation
Female
Gamma Rays*
Humans
Lymphocytes / radiation effects
Male
Middle Aged
Okadaic Acid / pharmacology
Radiation Dosage*
Radioactive Hazard Release*
Radiometry / methods*
Validation Studies as Topic
Chemical
Reg. No./Substance:
78111-17-8/Okadaic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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