Comparison of transcriptional responses in liver tissue and primary hepatocyte cell cultures after exposure to hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine.
BACKGROUND
Cell culture systems are useful in studying toxicological effects of chemicals such as Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), however little is known as to how accurately isolated cells reflect responses of intact organs. In this work, we compare transcriptional responses in livers of Sprague-Dawley rats and primary hepatocyte cells after exposure to RDX to determine how faithfully the in vitro model system reflects in vivo responses.


RESULTS
Expression patterns were found to be markedly different between liver tissue and primary cell cultures before exposure to RDX. Liver gene expression was enriched in processes important in toxicology such as metabolism of amino acids, lipids, aromatic compounds, and drugs when compared to cells. Transcriptional responses in cells exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours were different from those of livers isolated from rats 24 hours after exposure to 12, 24, or 48 mg/Kg RDX. Most of the differentially expressed genes identified across conditions and treatments could be attributed to differences between cells and tissue. Some similarity was observed in RDX effects on gene expression between tissue and cells, but also significant differences that appear to reflect the state of the cell or tissue examined.


CONCLUSIONS
Liver tissue and primary cells express different suites of genes that suggest they have fundamental differences in their cell physiology. Expression effects related to RDX exposure in cells reflected a fraction of liver responses indicating that care must be taken in extrapolating from primary cells to whole animal organ toxicity effects.
Perkins
Edward J
EJ
US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, MS, USA. edward.j.perkins@us.army.mil
Bao
Wenjun
W
Guan
Xin
X
Ang
Choo-Yaw
CY
Wolfinger
Russell D
RD
Chu
Tzu-Ming
TM
Meyer
Sharon A
SA
Inouye
Laura S
LS
D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012378:Rodenticides / Q000633:toxicity; D015533:Transcriptional Activation / Q000187:drug effects*; D014227:Triazines / Q000633:toxicity*
D012378:Rodenticides; D014227:Triazines; C009160:cyclonite