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Biomedical subjects

J N Dumont

Publications and source records attributed to J N Dumont.

At least 19 recordsLinked to original sources
PubMed2000

The effect of cadmium on oogenesis in Xenopus laevis.

Reproductive toxicity studies have historically centered on post-fertilization events. A thorough assessment of reproductive hazards to an organism should include all aspects of its life cycle. Cadmium is a teratogenic and carcinogenic heavy metal that occurs naturally in the environment but is also released anthropogenically. The effect of cadmium administration on oocyte development in Xenopus laevis was studied. Adult female Xenopus were injected in the dorsal lymph sac with cadmium chloride (CdCl2) at doses of 0.5, 0.75, 1.0, 3.0 or 5.0 mg/kg every other day for 21 days. Significant adverse effects of Cd on oocyte development were observed. The percentage of oocytes at all stages of oogenesis was decreased while the population of atretic oocytes increased dramatically (P < 0.0001). Numerous oocytes exhibited a speckled or mottled appearance and the incidence of completely atretic oocyte follicles increased. The observations indicate that Cd has the potential to significantly disrupt oogenesis and that examination of developing gametes may be a useful parameter for assessing the influence of environmental contaminants on reproductive capacity.

Animals↗
PubMed1998

Ground and surface water developmental toxicity at a municipal landfill: description and weather-related variation.

Contaminated groundwater poses a significant health hazard and may also impact wildlife such as amphibians when it surfaces. Using FETAX (Frog Embryo Teratogenesis Assay-Xenopus), the developmental toxicity of ground and surface water samples near a closed municipal landfill at Norman, OK, were evaluated. The groundwater samples were taken from a network of wells in a shallow, unconfined aquifer downgradient from the landfill. Surface water samples were obtained from a pond and small stream adjacent to the landfill. Surface water samples from a reference site in similar habitat were also analyzed. Groundwater samples were highly toxic in the area near the landfill, indicating a plume of toxicants. Surface water samples from the landfill site demonstrated elevated developmental toxicity. This toxicity was temporally variable and was significantly correlated with weather conditions during the 3 days prior to sampling. Mortality was negatively correlated with cumulative rain and relative humidity. Mortality was positively correlated with solar radiation and net radiation. No significant correlations were observed between mortality and weather parameters for days 4-7 preceding sampling.

Animals↗
PubMed1998

Phase III interlaboratory study of FETAX, Part 2: interlaboratory validation of an exogenous metabolic activation system for frog embryo teratogenesis assay--Xenopus (FETAX).

Interlaboratory validation of an exogenous metabolic activation system (MAS) developed for the alternative, short-term developmental toxicity bioassay, Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was performed with cyclophosphamide and caffeine. Seven study groups within six separate laboratories participated in the study in which three definitive concentration-response experiments were performed with and without the MAS in a side-by-side format for each chemical. Since both chemicals had been previously tested in FETAX, the test concentrations were provided to each laboratory prior to testing. Interlaboratory coefficient of variation (CV) values for unactivated cyclophosphamide (no MAS) were 15%, 15%, 29%, and 25% for the 96-hr LC50, 96-hr EC50 (malformation), Minimum Concentration to Inhibit Growth (MCIG), and Teratogenic Index (TI) values, respectively. Addition of the MAS increased the CV values of each endpoint at least 3.9-fold. Interlaboratory CV values for unactivated caffeine were 31%, 18%, 31%, and 46% for the 96-hr LC50, 96-hr EC50 (malformation), MCIG, and TI values, respectively. Addition of the MAS decreased the CV values of each respective endpoint by at least 1.6-fold. Results indicated that bioactivated toxicants may be prone to greater variability in response amongst laboratories than compounds, which are detoxified. Even though more variability was noted with activated cyclophosphamide, results were within interlaboratory variation expected for other aquatic-based bioassays. Thus, results from these studies warrant the continued use and further refinement of FETAX for alternative developmental toxicity assessment.

Abnormalities, Drug-Induced↗
PubMed1985

Egg envelopes in vertebrates.

As the material presented in this chapter was being collated, our existing perceptions about the basic similarities of vertebrate (and indeed most, if not all, invertebrate) egg envelopes became increasingly strengthened. Perhaps without exception, all vertebrate and invertebrate eggs acquire a "vitelline" envelope. Interestingly, its filamentous ultrastructure and chemical composition--basically protein and carbohydrate--is similar in all species as is its permeability to large molecules. Furthermore, many (if not all) of its functions are shared among the animal phyla as is its potential to become altered at the time of fertilization and, in its altered state, to provide a new set of modi operandi. It provides sperm receptors that are generally species specific and helps prevent polyspermy; it protects the developing embryo yet yields at the time of hatching. In most vertebrate eggs (including some mammals), a jelly or albumen coat is added to the vitelline envelope. These components may vary immensely in thickness, but again their basic chemical composition is common to all. The functions of these envelopes, while perhaps somewhat less clear than those of the vitelline envelope, are related to species-specific fertilization and to embryonic protection. Albumen serves a nutritional role--most clearly shown in the birds. Finally, the shell membrane and shell present in diverse groups contribute additional adaptations for embryo protection. Vertebrate egg envelopes, then, are basically similar; the modifications, including the addition of shell membranes and shells in some groups, reflect adaptations to differing reproductive strategies and to the environmental exigencies with which the egg must cope. With the growth of our understanding about the structure, chemistry, function, and evolution of egg envelopes new questions will continually be formulated. Many will be the same as those asked years ago but they will be answered with newer techniques and with greater insight.

Animals↗
PubMed1985

The embryotoxic and osteolathyrogenic effects of semicarbazide.

The osteolathyrogenic agent semicarbazide was assayed for its toxicity and teratogenicity using early embryos of the frog Xenopus laevis. The 96-h LC50 is 1504.20 mg/l while the 96-h EC50 is 76.28 mg/l. Embryo length is altered prior to the onset of other effects indicated by a reduction in stage of development. The major malformation is associated with the notochord where the notochordal sheath is reduced owing to the disruption in the maturation and/or deposition of the connective tissue fibers.

Abnormalities, Drug-Induced↗
PubMed1983

Thiosemicarbazide-induced osteolathyrism in metamorphosing Xenopus laevis.

Exposure of Xenopus laevis tadpoles to thiosemicarbazide (TSC), at concentrations from 10 to 75 mg/liter, causes an inhibition of metamorphosis and produces the classic manifestations of the experimental disease, osteolathyrism. Concentration-dependent effects of TSC exposure are observed in growth rate and in the severity of the osteolathyrogenic effect. Concentrations allowing the most rapid growth produce the more extreme osteolathyrogenic defects. Osteolathyrism in these animals is identical in characteristics to the condition described in a wide variety of vertebrate species. In Xenopus, osteolathyrism is expressed morphologically as anomalies in bone development, skeletal conformation, and abnormal connective tissue organization in the aorta wall. The underlying defect responsible for these observations is apparently a perturbation of collagen fiber formation and maturation, as evidenced ultrastructurally by aberrant distribution and packing of collagen fibers. It is suspected that TSC produces this effect by altering the availability of copper ion, a cofactor to lysyl oxidase, an essential enzyme for intermolecular cross-linking of procollagen. This step in collagen metabolism has been consistently implicated as the site of action of several osteolathyrogenic agents. Xenopus tadpoles present a classic response to this known osteolathyrogen and demonstrate a high degree of uniformity of response within the experimental groups. In view of the developmentally significant events accessible with this system and inherent logistic and economical advantages, the metamorphosing tadpole of Xenopus holds considerable potential for the experimental analysis of teratogenic agents and events.

Animals↗
PubMed1983

Structure activity relationships of selected naphthalene derivatives.

Twenty-two derivatives of naphthalene were assayed under an acute static regime with biological activity being monitored as population growth of Tetrahymena pyriformis. Activity varied over one log unit. Substituent constant structure-activity analyses revealed the model, log BR = 0.282Ha + 0.352 pi + 0.692F + 0.3341Xvsub - 0.326R + 0.027, to be best and to account for 85% of the variation in log BR (BR, biological response; Ha, hydrogen acceptance; pi, hydrophobic substituent constant; F, polar electronic substituent constant, 1Xvsub, substituent molar connectivity index; R, resonance electronic substituent constant). The Ha and pi parameters are the most important, accounting for 71% of the log BR variability.

Animals↗
PubMed1983

Toxic and teratogenic effects of chemical class fractions of a coal-gasification electrostatic precipitator tar.

Dimethyl sulfoxide slurries of a coal gasifier electrostatic precipitator tar and its chemical class fractions were assayed for their toxicity and teratogenicity using early embryos of the frog Xenopus laevis. Of the 5 tar fractions the ether-soluble base and polyaromatic were found to be the most teratogenic and the ether-soluble acid and ether-soluble base were the most toxic. The teratogenic effects of the raw tar suggest synergism. The toxic effects to newly metamorphosed froglets is 1-2 orders of magnitude less than those observed for embryos. Chemical analysis shows dihydroxybenzenes and organonitrogen compounds to be the major components of the acid and base fractions, respectively. The neutral fractions contain mainly alkyl-substituted two-ring hydrocarbons.

Abnormalities, Drug-Induced↗
PubMed1982

Embryotoxic and teratogenic effects of aqueous extracts of tar from a coal gasification electrostatic precipitator.

Aqueous extracts of tar from a coal gasification electrostatic precipitator were tested for its toxic and teratogenic potential in vitro on embryos of the amphibian Xenopus laevis. The 96-h LC50 and EC50 were determined to be 0.83% and 0.48%, respectively. The developmental stage of normal-appearing exposed embryos is not affected by increasing concentrations of the extract. Embryo growth, however, is significantly reduced at concentrations as low as 0.25%. Motility and pigmentation were effectively reduced relative to controls by extract concentrations of 0.5% and greater. Exposed embryos are shorter and stockier than controls. Malformations of head, eyes, viscera, and spine are common, and cartilage formation is abnormal. The epidermis is often hyperplastic, and large blisters occur over the somatic surface. The severity of abnormal development is directly related to the concentration of the toxicant to which the embryos are exposed. Chemical analysis shows that the aqueous extracts contain phenols, furans, monoaromatic and diaromatic hydrocarbons, and mono- and diazaarenes and/or monoaromatic amines.

Abnormalities, Drug-Induced↗
PubMed1981

Cortical vesicle breakdown in fertilized eggs of Fundulus heteroclitus.

A scanning and transmission electron microscope study has been made of the cortical alveoli of the egg of Fundulus heteroclitus. The study includes both unactivated eggs and fertilized eggs fixed at intervals of 1 second to 10 minutes after insemination. The alveoli appear to vary considerably in size, in contents, and in morphological aspects of their breakdown. As it undergoes dehiscence, each vesicle may form one or several openings in the egg surface; dense granules and particulate, fibrous, or membranous material, apparently in any combination, are liberated to the nascent perivitelline space. It appears that much of the excess membrane externalized during the reaction is strung out in threads and probably lost to the perivitelline space. The evidence does not suggest that the excess membrane either "dissolves" or is retrieved by the egg cytoplasm. That part of the cortical vesicle membrane which remains continuous with the oolemma gradually becomes microvillous and loses it morphological identity. Granules and particulate matter, presumably liberated from the cortical alveoli, are seen adhering to the inner surface of chorions removed from activated eggs. The micropyle appears to be sealed with similar material. Supernumerary sperm are observed inside the chorion in some instances. The cortical reaction appears to play secondary role in the prevention of polyspermy and to be somehow related to the subsequent formation of a normal embryonic blastodisc.

Animals↗
PubMed1981

Toxic and teratogenic effects of selected aromatic amines on embryos of the amphibian Xenopus laevis.

Evaluations of the toxic and teratogenic effects of four aromatic amines, acridine, aniline, pyridine, and quinoline, have been made on amphibian (Xenopus laevis) embryos. For toxicity testing, the embryos were divided into three groups according to stage of development: Group I were mid-blastulae, Group II were tailbud embryos, and Group III were swimming larvae. Of the amines tested, acridine and quinoline were the most toxic, followed by aniline and pyridine. Ninety six hr LC50 values for acridine, quinoline, aniline, and pyridine were 4.5, 95, 150, and 1090 mg/L, respectively, for Group III larvae. Except for acridine, where embryos in all three groups were about equally affected, those in Group II were less sensitive to the other amines than those in Groups I and III. Group I embryos were exposed to all four amines to determine their teratogenicity. The amines were ranked in order to decreasing teratogenicity: acridine, quinoline, aniline, and pyridine having 96-hr EC50 values of 2.4, 29, 370, and 1200 mg/L, respectively. Electron microscopic examination of Group III larvae exposed to these amines reveals pathology of the spinal cord and musculature. This damage was correlated with immobility of the larvae. The uptake of acridine was followed in larvae (Group III) exposed to 5 mg/L and was found to reach a maximum level of about 85 mg/g wet weight in about one hr. Depuration kinetics were characterized by a rapid loss of 70% of the total acridine within 45 min. Acridine was undetectable after two hr. These data suggest that acridine, aniline, and quinoline have toxic and teratogenic effects at sufficiently low concentrations as to make them potential environmental hazards.

Acridines↗
PubMed1980

Cytotoxic effects of sodium selenite on tadpoles (Xenopus laevis).

The cytotoxic effects of sodium selenite on developing tadpoles (Xenopus laevis) were examined by scanning, light, and electron microscopy. Selenium exposure resulted in disorganization, vacuolization, and swelling of the outer layer of epithelial cells in the tadpole epidermis. Examination of muscle cells in the somites revealed myofibril disorganization and cell degeneration. Mitochondria in both epithelial and muscle cells were swollen and showed loss of cristae. It is likely that sublethal exposures to selenium compounds result in cellular damage which could affect motility, and thus survival, over longer periods of time.

Animals↗
PubMed1980

Uptake, depuration, and distribution of selenium in Daphnia and its effects on survival and ultrastructure.

Selenium is an important essential nutritional trace element which has been shown to provide protection against certain other metal poisoning. However, it is a suspected carcinogen and teratogen. The uptake, depuration, and toxicity of selenium in Daphnia pulex have been examined. The LC50 at 48 and 96 hr for juvenile animals is 0.6 mg/L and 0.1 mg/L respectively, and for adults it is 1.3 mg/L and 0.5 mg/L respectively. Uptake in adult unfed animals is rapid, reaching a maximum at about 12 hr, but depuration is slow. In fed animals, uptake is slower, reaching a maximum at 96 hr, but initial depuration is followed by a slower prolonged loss. Localization in cells is primarily in the cytoplasmic compartment although evidence is presented which suggests nucleolar localization. Ultrastructural damage is detected by 16 hr after exposure and is initially confined to the mitochondria. Dense deposits accumulate in the mitochondrial matrices. The nature of these deposits is unknown; they may represent a calcium- or phosphate-selenium complex. With time, the mitochondria degenerate. It is clear that relatively low concentrations of selenium are toxic to these aquatic organisms and render them incapable of survival in the natural environment. Concentrations higher than those lethal to Daphnia can be expected, at least in local areas, from the burning or conversion of fossil fuels.

Animals↗
PubMed1980

Structure-toxicity relationships of selected nitrogenous heterocyclic compounds.

A series of eleven nitrogen-containing heterocyclic compounds, which may be potentially associated with aqueous effluents from coal conversion technologies, were examined to determine the relationships between their n-octanol/H2O partition coefficients, molecular weights, boiling points, and their toxicity monitored as reproduction impairment to Tetrahymena pyriformis. Toxicity increases linearly with increased partition coefficient, molecular weight, and boiling point. All of these parameters increase with increased alkyl and ring addition.

Animals↗
PubMed1979

Calcium-induced dehiscence of cortical granules in Xenopus laevis oocytes.

Microinjection of 0.1 microgram of Ca++ into Xenopus laevis oocytes induces breakdown of the cortical granules. The cortical granules disappeared in both full grown (Stage VI) and small growing (Stage IV) oocytes. Microinjection of Mg++, K+, or Na+ had no effect on cortical granules in either Stage IV or Stage VI oocytes. Small quantities (0.03 microgram) of Ca++ induced dehiscence of the cortical granules only in proximity to the injection site.

Animals↗