کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570247 1128576 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds : Species: Rat; Sex: Male; Route of administration: Water
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds : Species: Rat; Sex: Male; Route of administration: Water
چکیده انگلیسی

In this work, Quantitative Structure−Activity Relationship (QSAR) modelling was used as a tool for predicting the carcinogenic potency of a set of 39 nitroso-compounds, which have been bioassayed in male rats by using the oral route of administration. The optimum QSAR model provided evidence of good fit and performance of predicitivity from training set. It was able to account for about 84% of the variance in the experimental activity and exhibited high values of the determination coefficients of cross validations, leave one out and bootstrapping (q2LOO = 78.53 and q2Boot = 74.97). Such a model was based on spectral moments weighted with Gasteiger–Marsilli atomic charges, polarizability and hydrophobicity, as well as with Abraham indexes, specifically the summation solute hydrogen bond basicity and the combined dipolarity/polarizability. This is the first study to have explored the possibility of combining Abraham solute descriptors with spectral moments. A reasonable interpretation of these molecular descriptors from a toxicological point of view was achieved by means of taking into account bond contributions. The set of relationships so derived revealed the importance of the length of the alkyl chains for determining carcinogenic potential of the chemicals analysed, and were able to explain the difference between mono-substituted and di-substituted nitrosoureas as well as to discriminate between isomeric structures with hydroxyl-alkyl and alkyl substituents in different positions. Moreover, they allowed the recognition of structural alerts in classical structures of two potent nitrosamines, consistent with their biotransformation. These results indicate that this new approach has the potential for improving carcinogenicity predictions based on the identification of structural alerts.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 231, Issue 2, 1 September 2008, Pages 197–207
نویسندگان
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