Skip Navigation



ToxSci Advance Access published online on October 5, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi343
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
89/1/66    most recent
kfi343v1
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 Curtin, G. M.
Right arrow Articles by Slaga, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Curtin, G. M.
Right arrow Articles by Slaga, T. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 15, 2005
Accepted September 19, 2005

Carcinogenicity

Short-Term Biomarkers of Cigarette Smoke Condensate Tumor Promoting Potential in Mouse Skin

Geoffrey M. Curtin 1*, Margaret Hanausek 2, Zbigniew Walaszek 2, Robert Zoltaszek 2, James E. Swauger 1, Arnold T. Mosberg 1, and Thomas J. Slaga 2

1 Research and Development, R.J. Reynolds Tobacco Company, Winston-Salem, North Carolina, 27102
2 The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229

* To whom correspondence should be addressed.
Geoffrey M. Curtin, E-mail: curting{at}rjrt.com


  Abstract

Previous studies demonstrated that cigarette smoke condensates (CSCs) possessing significantly different tumorigenic potentials according to a standardized 30-week mouse skin tumor-promotion protocol could likewise be discriminated utilizing short-term indices of sustained hyperplasia and/or inflammation (Curtin et al., 2004, Toxicol. Sci. 81, 14-25). The current study employed a truncated initiation-promotion protocol to further evaluate CSC-induced hyperplasia, examining issues related to time course of induction, existence of a threshold and suitable dynamic range for detectable responses, and reversibility. Condensate application (9-36 mg "tar"/200-µL application, thrice-weekly for 3-15 wks) induced treatment-related increases for epidermal thickness, proliferative index as assessed by 5-bromo-2'-deoxyuridine (BrdU) labeling, and ornithine decarboxylase (ODC) expression. Interestingly, observed increases for interfollicular BrdU labeling and ODC expression were partially reversed but still elevated upon cessation of promotion, while increases within the perifollicular epidermis remained elevated at a level similar to that observed during CSC application. In particular, assessments based on perifollicular ODC expression would appear to provide a greater opportunity for test article discrimination based on a rapid time to induction, a low threshold and expanded dynamic range of responses, and the potential to account for irreversible changes. These findings are particularly intriguing based on reports suggesting that ODC expression may be necessary for tumor promotion and that mouse skin tumors originate primarily within the perifollicular epidermis.

Keywords: tumor promotion; hyperplasia; ornithine decarboxylase; perifollicular epidermis.
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.