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"Delayed death" phenomenon: A synergistic action of cyclophosphamide and exogenous DNA.
MedLine Citation:
PMID:  22227496     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Morbidity and mortality in mice were observed upon administration of exogenous DNA following their pre-treatment with a cytostatic agent cyclophosphamide. Upon intraperitoneal injections, the fragments of exogenous DNA reached bone marrow cells. These cells were also found to internalize up to 1800kb of exogenous DNA ex vivo. The 18-24h time frame represents a final stage in the repair of DNA double-strand breaks, so when exogenous DNA was administered within this critical period of time, pathological changes were observed in many target organs. Namely, bone marrow cells underwent a sustained increase in apoptosis. Copy number of B1 and B2 DNA repeats in bone marrow cells remained unchanged, whereas in the control group of animals their levels were significantly decreased. Finally, the bone marrow cells of moribund animals completely lacked lymphoid progenitors, yet the CD34+ hematopoietic stem cell counts were normal. Histopathology analysis suggested that mice died due to accidental involution of lymphoid organs combined with a systemic inflammatory process induced by massive administration of exogenous DNA and depletion of lymphoid lineage.
Authors:
Evgenia V Dolgova; Anastasia S Proskurina; Valeriy P Nikolin; Nelly A Popova; Ekaterina A Alyamkina; Konstantin E Orishchenko; Vladimir A Rogachev; Yaroslav R Efremov; Tatiana D Dubatolova; Anastasia V Prokopenko; Elena R Chernykh; Alexandr A Ostanin; Oleg S Taranov; Vladimir V Omigov; Stanislav N Zagrebelniy; Sergey S Bogachev; Mikhail A Shurdov
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-27
Journal Detail:
Title:  Gene     Volume:  -     ISSN:  1879-0038     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Affiliation:
Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090, Russia.
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