TY - JOUR
T1 - Short-term biomarkers of cigarette smoke condensate tumor promoting potential in mouse skin
AU - Curtin, Geoffrey M.
AU - Hanausek, Margaret
AU - Walaszek, Zbigniew
AU - Zoltaszek, Robert
AU - Swauger, James E.
AU - Mosberg, Arnold T.
AU - Slaga, Thomas J.
N1 - Funding Information:
Several of the authors, including the corresponding author, are employed by RJ Reynolds Tobacco Company (RJRT). In addition, this research was funded by RJRT; the funding organization does not have control over the resulting publication.
PY - 2006/1
Y1 - 2006/1
N2 - 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 (G. M. 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 weeks) 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.
AB - 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 (G. M. 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 weeks) 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.
KW - Hyperplasia
KW - Ornithine decarboxylase
KW - Perifollicular epidermis
KW - Tumor promotion
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U2 - 10.1093/toxsci/kfi343
DO - 10.1093/toxsci/kfi343
M3 - Article
C2 - 16207943
AN - SCOPUS:29544445612
VL - 89
SP - 66
EP - 74
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -