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

• Type: Article in International Scientific Journal
• Date: 2007

Authors

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

Journal

Title: Toxicology and Applied Pharmacology

Vol. 221

Pages: 189-202

ISSN: 0041-008X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 55 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14