Aspects of database construction and interrogation of relevance to the accurate prediction of rodent carcinogenicity and mutagenicity.
نویسنده
چکیده
Attempts to reconcile qualitative carcinogenicity databases with qualitative mutagenicity database continue to indicate that there is no useful relationship between mutagenicity/genotoxicity and rodent carcinogenicity. It is suggested that recognition of two classes of carcinogen, genotoxic and nongenotoxic, is the first step in finding meaningful correlations between the above parameters. This then leads to purposeful intervention into the databases, including rejecting low quality data, abandoning some assays from the database, and clustering certain end points as repetitive rather that independent of each other. Seeking specific correlations within a focused database may yield knowledge from the current wealth of information. The effort required to build databases, particularly quantitative ones, has so far prevented the equally arduous task of their correct interrogation. Preliminary indications are the mutagenicity is closely correlated with genotoxic carcinogenesis and completely independent of nongenotoxic carcinogenesis.
منابع مشابه
Running Title: lazar Carcinogenicity Predictions Lazy Structure-Activity Relationships (lazar) for the Prediction of Rodent Carcinogenicity and Salmonella Mutagenicity
lazar is a new tool for the prediction of toxic properties of chemical structures. It derives predictions for query structures from a database with experimentally determined toxicity data. lazar generates predictions by searching the database for compounds that are similar with respect to a given toxic activity and calculating the prediction from their activities. Apart form the prediction, laz...
متن کاملPrediction of rodent carcinogenicity for 30 chemicals.
Predictions of carcinogenic activity are made for 30 chemicals currently being assessed for rodent carcinogenicity by the U.S. National Toxicology Program. The predictions are based upon the chemical structure, the anticipated or reported mutagenicity, and the reported sub-chronic toxicity of each chemical. It is predicted that 13 chemicals will be noncarcinogenic to rodents, that 7 will be gen...
متن کاملA Novel Strategy to Predict Carcinogenicity of Antiparasitics Based on a Combination of DNA Lesions and Bacterial Mutagenicity Tests
Genotoxicity and carcinogenicity testing of pharmaceuticals prior to commercialization is requested by regulatory agencies. The bacterial mutagenicity test was considered having the highest accuracy of carcinogenic prediction. However, some evidences suggest that it always results in false-positive responses when the bacterial mutagenicity test is used to predict carcinogenicity. Along with maj...
متن کاملThe genetic toxicity database of the National Toxicology Program: evaluation of the relationships between genetic toxicity and carcinogenicity.
The database of the U.S. National Toxicology Program has been developed over approximately two decades, principally focused on substances evaluated for carcinogenicity in rodent bioassays. These assays generally provide data on the relative toxicity and carcinogenicity of chemicals based upon discrete subchronic (13 week) and chronic (104 week) exposures. A major value of these data are that th...
متن کاملCarcinogenicity of the aromatic amines: from structure-activity relationships to mechanisms of action and risk assessment.
Aromatic amines represent one of the most important classes of industrial and environmental chemicals: many of them have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants. Their toxicity has been studied also with quantitative structure-activity relationship (QSAR) methods: these studies are potentially suitable for investigating mechanisms of action and for estimating...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Environmental Health Perspectives
دوره 96 شماره
صفحات -
تاریخ انتشار 1991