Optimization of an Exogenous Metabolic Activation System for Fetax. Ii. Preliminary Evaluation

Abstract

The developmental toxicities of five test compounds including carbon tetrachloride, urethane, phenacetin, parathion, and chloroform, were evaluated using Frog Embryo Teratogenesis Assay--Xenopus (FETAX), with minor modification. Post-isolation mixtures of differently-induced rat liver microsomes (phenobarbital- (PB), beta-naphthoflavone- (beta-NF), and isoniazid- (INH)-induced preparations) were co-cultured directly with X. laevis embryos. Results from these studies suggest that the Aroclor 1254-induced MAS could effectively be replaced by a mixed lot of PB-, beta-NF-, and INH-induced rat liver microsomes. Each of the test materials were found to be developmentally toxic when bioactivated by the mixed MAS.

Aryl Hydrocarbon Receptors in the Frog Xenopus laevis: Two AhR1 Paralogs Exhibit Low Affinity for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD)

“…Substantial effort has been invested by research groups (e.g. Bantle et al 1994;Bantle et al 1996;Bantle et al 1999;Bantle et al 1990;Fort et al 1989;Fort et al 2001a;Fort et al 2001b;Fort et al 1998;Fort et al 1995) and government panels (FETAX 2000) to validate this test and to adapt it for use in the screening of chemicals and environmental samples. With the discovery of two X. laevis AHRs with low affinity for TCDD, this study identifies an important mechanistic basis for the differences in HAH toxicity between the frog embryo model and other vertebrates, including humans, which should help evaluate and refine the use of FETAX in conjunction with HAH-containing samples.…”

“…With the discovery of two X. laevis AHRs with low affinity for TCDD, this study identifies an important mechanistic basis for the differences in HAH toxicity between the frog embryo model and other vertebrates, including humans, which should help evaluate and refine the use of FETAX in conjunction with HAH-containing samples. Low affinity of X. laevis AHRs for other ligands might also explain the low toxicity of polynuclear aromatic hydrocarbons in FETAX and underlie the historically reported low expression levels of Cytochromes P-450 during early frog development (Bantle 1996;Bantle et al 1991;Fort et al 1991;Fort et al 2001a;Fort et al 2001b;ASTM 1998).…”

Gene Expression in Xenopus Embryos After Methylmercury Exposure: A Search for Molecular Biomarkers

“…Chem. 21, 2002 2735 to protocol modification with respect to maternal exposure, length of assay, change of endpoint, and so on [16][17][18][19][20]. The FETAX assay appears to satisfy the requirements of reliability, reproducibility, and low cost, and it represents a good alternative to the use of in vivo procedures in mammals for screening chemicals [21].…”

“…21, 2002 2735 to protocol modification with respect to maternal exposure, length of assay, change of endpoint, and so on [16][17][18][19][20]. Toxicol.…”

Gene expression in Xenopus embryos after methylmercury exposure: A search for molecular biomarkers

“…As a biological system, we have chosen Xenopus laevis embryos, as Xenopus is a well‐known model organism and also because we could take advantage of the results obtained by FETAX to choose suitable CH 3 HgCl concentration and exposure time [6]. The FETAX assay [14,15] is a powerful and flexible bioassay for developmental toxicants and is amenable to protocol modification with respect to maternal exposure, length of assay, change of endpoint, and so on [16–20]. The FETAX assay appears to satisfy the requirements of reliability, reproducibility, and low cost, and it represents a good alternative to the use of in vivo procedures in mammals for screening chemicals [21].…”