Skip Navigation



ToxSci Advance Access published online on May 5, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh157
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
80/2/258    most recent
kfh157v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Smith, M. V.
Right arrow Articles by Portier, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, M. V.
Right arrow Articles by Portier, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received December 15, 2003
Accepted April 20, 2004

Carcinogenicity

Application of a Statistical Dynamic Model Investigating the Short-Term Cellular Kinetics Induced by Riddelliine, a Hepatic Endothelial Carcinogen

Marjo V. Smith 1*, Abraham Nyska 2, Chris Portier 2

1 Constella Health Sciences, 2605 Meridian Parkway, Durham, North Carolina 27713
2 National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27713

* To whom correspondence should be addressed. E-mail: msmith{at}constellagroup.com.


  Abstract

In recent studies, riddelliine, a pyrrolizidine alkaloid, was found to increase rates of replication and apoptosis and induce hemangiosarcoma in the liver of rats and mice. To analyze DNA replication and apoptosis data taken from the same animals, we have developed a predictive mathematical model for describing BrdU labeling and apoptotic processes. The model allows the incorporation of simple diurnal patterns in cellular kinetics and is applied to data on hepatocytes and endothelial cells taken from riddelliine exposed rats. Predictions from the model were used with multivariable nonlinear regression techniques to estimate replication and apoptotic rate constants for both cell types and all treatment groups. Hypothesis tests were used with the predicted rates to separate the competing effects of riddelliine on replication and apoptosis of hepatocytes and endothelial cells as well as compare replication rates between cell types. That estimated replication rates were found to be significantly higher for endothelial cells supports the supposition of induction of hemangiosarcoma by riddelliine in the liver.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.