Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Borniger, J. C., Walker Ii, W. H., Gaudier-Diaz, M. M., Stegman, C. J., Zhang, N., Hollyfield, J. L., Nelson, R. J., DeVries, A. C. (January 2017) Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy. Sci Rep, 7. p. 41220. ISSN 2045-2322 (Electronic)2045-2322 (Linking)

[thumbnail of srep41220.pdf]
srep41220.pdf - Published Version

Download (5MB) | Preview
URL: https://www.ncbi.nlm.nih.gov/pubmed/28117419
DOI: 10.1038/srep41220


Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > biological clock
diseases & disorders > cancer > drugs and therapies > chemotherapy
diseases & disorders > inflammation > cytokines
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Borniger lab
Depositing User: Adrian Gomez
Date: 24 January 2017
Date Deposited: 06 Jan 2020 14:21
Last Modified: 06 Jan 2020 14:21
PMCID: PMC5259749
Related URLs:
URI: https://repository.cshl.edu/id/eprint/38863

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving