In vitro erythropoiesis from bone marrow-derived progenitors provides a physiological assay for toxic and mutagenic compounds

J. Shuga, J. Zhang, L. D. Samson, H. F. Lodish, L. G. Griffiths

Research output: Contribution to journalArticle

Abstract

The goal of this study was to create an in vitro cell culture system that captures essential features of the in vivo erythroid micronucleus (MN) genotoxicity assay, thus enabling increased throughput and controlled studies of the hematopoietic DNA damage response. We show that adult bone marrow (BM) cultures respond to erythropoietin, the principal hormone that stimulates erythropoiesis, with physiological erythropoietic proliferation, differentiation, and enucleation. We then show that this in vitro erythropoietic system clearly signals exposure to genotoxicants through erythroid MN formation. Furthermore, we determined that DNA repair-deficient (MGMT -/-) BM displayed sensitivity to genotoxic exposure in vivo compared with WT BM and that this phenotypic response was reflected in erythropoietic cultures. These findings suggest that this in vitro erythroid MN assay is capable of screening for genotoxicity on BM in a physiologically reflective manner. Finally, responses to genotoxicants during erythroid differentiation varied with exposure time, demonstrating that this system can be used to study the effect of DNA damage at specific developmental stages.

Original languageEnglish (US)
Pages (from-to)8737-8742
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number21
DOIs
StatePublished - May 22 2007
Externally publishedYes

Fingerprint

Erythropoiesis
Poisons
Bone Marrow
Micronucleus Tests
DNA Damage
DNA Repair-Deficiency Disorders
Erythropoietin
Cell Culture Techniques
Hormones
In Vitro Techniques

Keywords

  • DNA damage and repair
  • Genotoxicity
  • Hematopoiesis
  • In vitro toxicity screens

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

In vitro erythropoiesis from bone marrow-derived progenitors provides a physiological assay for toxic and mutagenic compounds. / Shuga, J.; Zhang, J.; Samson, L. D.; Lodish, H. F.; Griffiths, L. G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 21, 22.05.2007, p. 8737-8742.

Research output: Contribution to journalArticle

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