The concept of negativity in experimental carcinogenesis |
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| Affiliation: | 1. Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, 190006, India;2. Plant Biotechnology and Molecular Biology Lab, CSIR-Indian Institute of Integrative Medicine, Srinagar, 190005, India;3. Department of Biotechnology, School of Biosciences and Biotechnology, BGSB University, Rajouri, India;1. Lethbridge Research Centre, Agriculture and Agri-Food Canada, Lethbridge, Alberta, Canada T1J 4B1;2. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5;3. University for Development Studies, P.O. Box TL 1882, Tamale, Ghana;4. Pioneer Hi-Bred International Inc., Johnson, IA, USA;1. Modeling and Informatics, Merck & Co., Inc., Boston, MA, USA;2. Scientific Modeling Platforms, Merck & Co., Inc., Boston, MA, USA;3. QuickBase, Inc., Cambridge, MA, USA;4. Lead Discovery and Optimization, Bristol-Myers Squibb, Pennington, NJ, USA;5. Infectious Disease, Merck & Co., Inc., West Point, PA, USA;6. Discovery Chemistry, Merck & Co., Inc., West Point, PA, USA;7. Modeling and Informatics, Merck & Co., Inc., Kenilworth, NJ, USA;8. Modeling and Informatics, Merck & Co., Inc., West Point, PA, USA;9. Modeling and Informatics, Merck & Co., Rahway, NJ, USA;10. Scientific Information Management, Merck & Co., Inc., Boston, MA, USA |
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| Abstract: | The problems that arise in the interpretation of experimental data on chemical carcinogenesis are addressed. In particular, the difficulties in demonstrating negative results are shown to present problems in delineating carcinogens from noncarcinogens. The use of the virtually safe dose estimated under the assumption of low dose linearity is shown to lead to potentially anomalous results if used indiscriminately in bioassays in which no statistically significant increase in tumor occurrence is induced. It is suggested that there is a need to establish an operational definition of negativity in carcinogenesis, with the realization that this definition may be revised in light of new information. The establishment of negativity in aligning data from positive and negative experiments and in considering possible thresholds is also discussed. |
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