Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

• Tipo: Artigo em Revista Científica Internacional
• Data: 2007

Autores

Aliuska Morales Helguera (Autor) Outra; Maykel Perez Gonzalez (Autor) Outra; Maria Natalia D S Cordeiro (Autor) FCUP; Miguel Angel Cabrera Perez (Autor) Outra

Revista

Título: Toxicology and Applied Pharmacology

Vol. 221

Páginas: 189-202

ISSN: 0041-008X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 52 Citações

Scopus - 55 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-004-9ZD

DOI: 10.1016/j.taap.2007.02.021

Abstract (EN): Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here - Quantitative Structure-Activity Relationship (QSAR) are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions - expressed as fragment contributions to the carcinogenic activity - that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14