Biomedical subjects

E L Stover

Publications and source records attributed to E L Stover.

23 records · Page 2Linked to original sources

PubMedDate not supplied

Preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function using Xenopus laevis.

Short-term static-renewal studies were performed on Xenopus laevis embryos with 16 selected test materials from day 50 (stage 60) to day 64 (stage 66) (14-day test) to evaluate effects on tail resorption and thyroid function. Of the 16 test materials, nine were found to inhibit significantly the rate of tail resorption, four were found to stimulate metamorphosis and three had no appreciable effect on the rate of metamorphosis. In an effort to determine if the morphological effects observed were related to alteration in thyroid activity, measurement of triiodothyronine (T3) in the test organisms and coadministration studies using thyroxine (agonist) or propylthiouracil (antagonist) were performed based on the morphological response noted during tail resorption. Of the nine compounds found to inhibit the rate of tail resorption, six were found to reduce the levels of T3. In each case, the inhibitory response could be at least partially alleviated by the co-administration of thyroxine. Larvae exposed to the four stimulatory agents had somewhat elevated levels of T3 and were responsive to propylthiouracil antagonism. These results suggest that 12 of the 14 compounds tested in this study that altered the rate of tail resorption did so via the thyroid axis. Overall, the X. laevis model appeared to be a suitable system for evaluating the impact of environmental agents and chemical products on thyroid function.

Animals↗

PubMedDate not supplied

Ecological hazard assessment of aqueous soil extracts using FETAX. Frog Embryo Teratogenesis Assay--Xenopus.

Frog Embryo Teratogenesis Assay--Xenopus (FETAX) testing of a series of diverse hazardous waste-site soil samples was performed to evaluate the efficacy of FETAX as a rapid developmental toxicity screening tool for environmental hazard assessment. Soil samples were collected from six different hazardous waste sites, three from eastern and three from western Washington State. The type of waste site samples studied, based on the contaminants identified, included: heavy metals (2), polynuclear aromatic hydrocarbons, petroleum products (2) and organochlorine pesticides. Three to five samples from each site representing baseline and increasing levels of contamination were collected. Aqueous extracts of the soil samples were prepared and used for FETAX studies. Samples collected from the polynuclear aromatic hydrocarbon- and petroleum product-contaminated sites induced greater levels of embryolethal effects, although embryonic malformation was also observed. The metal-contaminated sites induced greater levels of embryonic malformation, but induced less embryolethality than the other samples evaluated. The organochlorine pesticide-contaminated site samples caused significant levels of embryonic deformities but failed to induce embryolethal effects. Results from these studies suggested that FETAX was sensitive enough to detect low levels of developmental toxicants but robust enough to be suitable for aqueous soil extract testing. FETAX may be used as a component of a battery of tests designed to assess potential ecological hazard.

Animals↗

PubMedDate not supplied

Evaluation of a reproductive toxicity assay using Xenopus laevis: boric acid, cadmium and ethylene glycol monomethyl ether.

Cadmium (Cd), boric acid (BA) and ethylene glycol monomethyl ether (EGME) were evaluated for reproductive and developmental toxicity in Xenopus laevis. Eight reproductively mature adult male and eight superovulated female Xenopus laevis were exposed to at least five separate sublethal concentrations of each material via the culture water for a period of 30 days. Four respective pairs were mated and the offspring evaluated for developmental effects; an evaluation of reproductive status was performed on the remaining four specimens. Ovary pathology, oocyte count, oocyte maturity and maturation capacity (germinal vesicle breakdown, GVBD) and necrosis were evaluated in the female, whereas testis pathology, sperm count, dysmorphology and motility were studied in the male. Based on this assessment, each test material exerted reproductive toxicity in Xenopus laevis, but with varying potencies. Adult female exposure to Cd and EGME particularly, and to a lesser extent to BA, resulted in transgenerational toxicity to the developing progeny. Further, this model appears to be a useful tool in the initial assessment and prioritization of potential reproductive toxicants for further testing.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Effects of pond water, sediment and sediment extract samples from New Hampshire, USA on early Xenopus development and metamorphosis: comparison to native species.

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 14-/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo-larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co-administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo-larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine.

Animals↗

PubMedDate not supplied

Evaluation of the developmental toxicity of benzo[a]pyrene and 2-acetylaminofluorene using Xenopus: modes of biotransformation. Stover Group.

The developmental toxicities of benzo[a]pyrene (BAP) and 2-acetylaminofluorene (AAF) were evaluated using FETAX (Frog Embryo Teratogenesis Assay-Xenopus). Young X. laevis embryos were exposed to these two compounds 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 cimetidine (CIM), ellipticine (ELL), or alpha-napthoflavone (alpha-N) to selectively modulate cytochrome P-450 activity. Bioactivation of both of these compounds was indicated by increased developmental toxicity observed in MAS tests. Results obtained in treated MAS tests indicated that BAP was predominantly activated by Cytochrome P-450 isozyme CYP1A1. AAF bioactivation was shown to be only partly mediated by CYP1A1/2. Detoxification pathways for these two compounds were investigated by treatment of the MAS with cyclohexene oxide (CHO) and diethyl maleate (DM) to inhibit the epoxide hydroxylase and glutathione conjugation pathways, respectively. Results indicated that epoxide hydroxylase was primarily responsible for the detoxification of BAP, with glutathione conjugation playing a secondary role. Detoxification of AAF by these two pathways was not indicated.

2-Acetylaminofluorene↗