6533b7d1fe1ef96bd125ce68

RESEARCH PRODUCT

Covalent binding of drug metabolites to DNA ? a tool of predictive value?

Reinhold J. LaibH. M. Bolt

subject

DrugHealth Toxicology and Mutagenesismedia_common.quotation_subjectLiver NeoplasmsDrug Evaluation PreclinicalCovalent bindingDNAGeneral MedicineIn Vitro TechniquesToxicologyPredictive valueMolecular biologyRatschemistry.chemical_compoundLiverchemistryBiochemistryCovalent bondCarcinogensAnimalsStandard testDNACarcinogenDrug metabolismmedia_common

description

The presently available data suggest at least some correlation between covalent binding of drug metabolites to DNA and carcinogenicity of that drug. More data, however, are needed to establish the predictability of covalent DNA binding assays for extrahepatic cancer. A covalent binding assay requires administration of radioactively labelled compound to the experimental animals; the availability of labelled compound and requirements as to radiochemical purity, chemical and biochemical stability are limiting the applicability of this procedure. Many technical pitfalls accompany covalent DNA binding assays. It is concluded that at the present time DNA binding assays do not represent routine procedures within a standard test battery for carcinogenicity, but are invaluable for more in-depth research which probably follows routine testing.

https://doi.org/10.1007/bf00361255