Evaluation of the developmental toxicity of theophylline, dimethyluric acid, and methylxanthine metabolites using Xenopus

Drug and Chemical Toxicology
D J FortJ A Bantle

Abstract

The developmental toxicities of theophylline and theophylline metabolites were evaluated using FETAX (Frog Embryo Teratogenesis Assay - Xenopus). Young X. laevis embryos were exposed to theophylline, 1-methylxanthine, 3-methylxanthine, or 1, 3-dimethyluric acid in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO), cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450 activity. Addition of the MAS and CIM-MAS reduced the developmental toxicity of theophylline. Addition of the ELL- or CO-inhibited MAS did not reduce the developmental toxicity of theophylline. Addition of the intact MAS did not alter the developmental toxicity of 1-methyl- or 3-methylxanthine which were slightly more developmentally toxic on an equimolar basis than theophylline itself. 1, 3-dimethyluric acid was not developmentally toxic at maximum soluble concentrations in 1% (V/V) DMSO. Results from these studies suggested that P-450, specifically ELL-inhibited P-450 (aryl hydrocarbon hydroxylase) may have been responsible for detoxification of theophylline and that 1, 3 dimethyluric acid represented ...Continue Reading

References

Jan 1, 1992·Drug and Chemical Toxicology·D J FortJ A Bantle
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Jan 1, 1988·Teratogenesis, Carcinogenesis, and Mutagenesis·D A DawsonJ A Bantle
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Jan 1, 1993·Teratogenesis, Carcinogenesis, and Mutagenesis·D J FortJ A Bantle

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Citations

Mar 20, 2003·Drug and Chemical Toxicology·Douglas J FortBrody O Buzzard
Nov 20, 2004·Journal of Applied Toxicology : JAT·Douglas J FortClinton D Spaulding
Feb 19, 2000·Teratogenesis, Carcinogenesis, and Mutagenesis·D J FortJ K Lemen
May 17, 2002·Journal of Applied Toxicology : JAT·Douglas J Fort, Robbin R Paul
Mar 2, 1999·Biological Trace Element Research·D J FortF J Murray
Feb 23, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xiaohua ZhaoLing Yang

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