Thalidomide and metabolites: indications of the absence of 'genotoxic' carcinogenic potentials.
Because of the reintroduction into human therapeutics of thalidomide, a recognized developmental toxicant in humans, there has been concern about its potential for inducing other health effects as well. The present study is concerned with the possible mutagenicity and carcinogenicity of this chemical. Using the expert system, META, a series of putative metabolites of thalidomide was generated. In addition to the known or hypothesized metabolites of thalidomide (N=12), a number of additional putative metabolites (N=131) were identified by META. The structures of these chemicals were subjected to structure-activity analyses using predictive CASE/MULTICASE models of developmental toxicity, rodent carcinogenicity and mutagenicity in Salmonella. While thalidomide and some of its putative metabolites were predicted to be developmental toxicants, none of them were predicted to be rodent carcinogens. Putative metabolites containing the hydroxamic acid or hydroxylamine moieties were predicted to be mutagens. None of the 'known' metabolites of thalidomide contained these reactive moieties. Whether such intermediates are indeed generated or whether they are generated and are either unstable in the presence of oxygen or react rapidly with nucleophiles is unknown.[1]References
- Thalidomide and metabolites: indications of the absence of 'genotoxic' carcinogenic potentials. Zhu, X., Zhang, Y.P., Klopman, G., Rosenkranz, H.S. Mutat. Res. (1999) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg