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SAR QSAR Environ Res ; 23(7-8): 775-95, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23066888

RESUMEN

SAR models were developed for 12 rat tumour sites using data derived from the Carcinogenic Potency Database. Essentially, the models fall into two categories: Target Site Carcinogen-Non-Carcinogen (TSC-NC) and Target Site Carcinogen-Non-Target Site Carcinogen (TSC-NTSC). The TSC-NC models were composed of active chemicals that were carcinogenic to a specific target site and inactive ones that were whole animal non-carcinogens. On the other hand, the TSC-NTSC models used an inactive category also composed of carcinogens but to any/all other sites but the target site. Leave one out (LOO) validations produced an overall average concordance value for all 12 models of 0.77 for the TSC-NC models and 0.73 for the TSC-NTSC models. Overall, these findings suggest that while the TSC-NC models are able to distinguish between carcinogens and non-carcinogens, the TSC-NTSC models are identifying structural attributes that associate carcinogens to specific tumour sites. Since the TSC-NTSC models are composed of active and inactive compounds that are genotoxic and non-genotoxic carcinogens, the TSC-NTSC models may be capable of deciphering non-genotoxic mechanisms of carcinogenesis. Together, models of this type may also prove useful in anticancer drug development since they essentially contain chemical moieties that target a specific tumour site.


Asunto(s)
Estructuras Animales/efectos de los fármacos , Carcinógenos/química , Carcinógenos/farmacología , Neoplasias/inducido químicamente , Relación Estructura-Actividad , Animales , Ratas
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