ToxSci Advance Access originally published online on May 24, 2004
Toxicological Sciences 2004 81(1):14-25; doi:10.1093/toxsci/kfh172
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences vol. 81 no. 1 © Society of Toxicology 2004; all rights reserved.
Short-Term In Vitro and In Vivo Analyses for Assessing the Tumor-Promoting Potentials of Cigarette Smoke Condensates
* Research and Development, R. J. Reynolds Tobacco Company, Winston-Salem, North Carolina 27102, and AMC Cancer Research Center, Denver, Colorado 80214
Received February 2, 2004; accepted May 7, 2004
Previous studies found that repeated application of smoke condensate from tobacco-burning reference cigarettes to chemically initiated SENCAR mouse skin promoted the development of tumors in a statistically significant and dose-dependent manner, while condensate from prototype cigarettes that primarily heat tobacco promoted statistically fewer tumors. Based on the recognized correlation between sustained, potentiated epidermal hyperplasia and tumor promotion, we conducted tests to examine the utility of selected short-term analyses for discriminating between condensates exhibiting significantly different promotion activities. In vitro analyses assessing the potential for inducing cytotoxicity (ATP bioluminescence) or free radical production (cytochrome c reduction, salicylate trapping) demonstrated significant reductions when comparing condensate collected from prototype cigarettes to reference condensate. Short-term in vivo analyses conducted within the context of a mouse skin, tumor-promotion protocol (i.e., comparative measures of epidermal thickness, proliferative index, myeloperoxidase activity, leukocyte invasion, mutation of Ha-ras, and formation of modified DNA bases) provided similar results. Reference condensate induced statistically significant and dose-dependent increases (relative to vehicle control) for nearly all indices examined, while prototype condensate possessed a significantly reduced potential for inducing changes that we regarded as consistent with sustained epidermal hyperplasia and/or inflammation. Collectively, these data support the contention that selected short-term analyses associated with sustained hyperplasia and/or inflammation are capable of discriminating between smoke condensates with dissimilar tumor-promotion potentials. Moreover, our results suggest that comparative measures of proliferative index and myeloperoxidase activity, both possessing favorable correlation coefficients relative to tumor formation (i.e., 
0.95 after 8 or 12 weeks of promotion), may constitute reasonable end points for further investigation.
Key Words: tumor promotion; short-term analyses; sustained epidermal hyperplasia; inflammation.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. M. Curtin, M. Hanausek, Z. Walaszek, R. Zoltaszek, J. E. Swauger, A. T. Mosberg, and T. J. Slaga Short-Term Biomarkers of Cigarette Smoke Condensate Tumor Promoting Potential in Mouse Skin Toxicol. Sci., January 1, 2006; 89(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Zhong, Y.-M. Zhou, G. C. Douglas, H. Witschi, and K. E. Pinkerton MAPK/AP-1 signal pathway in tobacco smoke-induced cell proliferation and squamous metaplasia in the lungs of rats Carcinogenesis, December 1, 2005; 26(12): 2187 - 2195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sandstrom and B. Lundback Tobacco smoke: old foe more important for asthma than commonly appreciated? Eur. Respir. J., November 1, 2004; 24(5): 720 - 721. [Full Text] [PDF]
|
|