RESUMEN
Oil refineries inadvertently deposit a variety of complex mixtures of organic hydrocarbons and heavy metals in the soil, many of which are thought to be potent immunotoxicants. Terrestrial ecosystems such as this have not been adequately investigated with respect to wild rodent populations. The primary objective of this study was to use mesocosms to assess the immunotoxicity risks to feral small mammal populations associated with soils contaminated with petroleum refinery wastes. A series of 4-week and 8-week exposure trials using laboratory raised cotton rats (Sigmodon hispidus) were conducted in situ on three contaminated and three reference sites on the Oklahoma Refining Company Superfund Waste Site, Cyril, Oklahoma. Cotton rats exposed to these soils showed significant alterations in selected morphological traits, in vivo humoral immune responses, complement activity, and macrophage activity. However, immune alterations were not great, suggesting that resident small mammals may be a better biomonitoring choice than using mesocosms.
Asunto(s)
Monitoreo del Ambiente , Residuos Peligrosos , Inmunotoxinas/toxicidad , Petróleo , Contaminantes del Suelo , Animales , Formación de Anticuerpos , Pruebas Hematológicas , Inmunidad Celular , Masculino , Medición de Riesgo , SigmodontinaeRESUMEN
Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.
Asunto(s)
Anuros/anomalías , Ectromelia/veterinaria , Miembro Posterior/anomalías , Teratógenos/farmacología , Contaminantes Químicos del Agua/toxicidad , Animales , Ectromelia/inducido químicamente , Ectromelia/epidemiología , Monitoreo del Ambiente , Monitoreo Epidemiológico , Pruebas de Toxicidad/normas , Xenopus laevis/anomalíasRESUMEN
The developmental toxicities of caffeine and 13 metabolites, including theophylline, and paraxanthine and a synthetic methylxanthine analogue 3-isobutyl-methylxanthine (IBMX) were evaluated using the Frog Embryo Teratogenesis Assay Xenopus (FETAX). Young X. laevis embryos were exposed to these compounds in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS). Results obtained from these studies indicated that relative teratogenic potencies of caffeine and each of its di- and monomethylxanthine metabolites were similar. Representatives of both the substituted uric and uracil metabolites were less developmentally toxic on an equimolar basis than the methylxanthines, suggesting that they may have represented detoxification metabolites. IBMX, a phosphodiesterase inhibitor also known to be an adenosine receptor antagonist, was the most potent developmental toxicant of the materials evaluated. In conclusion, none of the caffeine metabolites tested was found to be significantly more potent than caffeine itself in the FETAX assay.
Asunto(s)
Cafeína/toxicidad , Estimulantes del Sistema Nervioso Central/toxicidad , Embrión no Mamífero/efectos de los fármacos , Xenopus/embriología , Anomalías Inducidas por Medicamentos/etiología , Animales , Biotransformación , Embrión no Mamífero/anomalías , Femenino , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Frog embryo teratogenesis assay--Xenopus (FETAX) was utilized as a model system to evaluate the effects on embryo-larval development at various low boron (B) exposure levels in the culture media. Concentrations tested ranged from < 1 to 5000 microg B/L. A statistically significant (P < 0.05) increase in malformations was observed at < or = 3 microg B/L, but not at the greater concentrations. Abnormal development of the gut, craniofacial region and eye, visceral edema, and kinking of the tail musculature (abnormal myotome development) and notochord were observed. In subsequent studies, adult frogs were maintained for 28 d on two diets: (1) low B (LB, 62 microg B/kg) or (2) boric acid supplemented (BA, 1851 microg B/kg); the frogs were subsequently mated, and their offspring were cultured in media containing various levels of B. Results of the 28-d depletion studies indicated that frogs maintained under LB conditions produced a greater proportion of (1) necrotic eggs and (2) fertilized embryos, which abnormally gastrulated at a greater rate and were substantially less viable than embryos from frogs fed the BA diet. Malformations similar to those seen in the initial study were observed in embryos from the B-depleted adults maintained in an LB environment; 28 d on the LB diet enhanced the incidence of malformations associated with the LB culture media. These abnormalities were not observed in embryos cultured in > or = 4 microg B/L from adults cultured on the BA diet. These studies showed that insufficient B reproducibly interfered with normal Xenopus laevis development during organogenesis, substantially impaired normal reproductive function in adult frogs, and thus represent the first studies demonstrating the nutritional essentiality of B in an amphibian species.
Asunto(s)
Boro/deficiencia , Anomalías Congénitas/etiología , Reproducción/efectos de los fármacos , Xenopus laevis/fisiología , Animales , Boro/administración & dosificación , Cobre/farmacología , Dieta , Suplementos Dietéticos , Embrión no Mamífero/efectos de los fármacos , Femenino , Deformidades Congénitas de las Extremidades/etiología , Masculino , Xenopus laevis/embriología , Zinc/farmacologíaRESUMEN
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.
Asunto(s)
2-Acetilaminofluoreno/toxicidad , Benzo(a)pireno/toxicidad , Carcinógenos/toxicidad , Desarrollo Embrionario y Fetal/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Benzoflavonas/farmacología , Biotransformación , Cimetidina/farmacología , Ciclohexanos/farmacología , Ciclohexenos , Citocromo P-450 CYP1A1/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Elipticinas/farmacología , Activación Enzimática/efectos de los fármacos , Epóxido Hidrolasas/antagonistas & inhibidores , Glutatión/metabolismo , Antagonistas de los Receptores H2 de la Histamina/farmacología , Masculino , Maleatos/farmacología , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Ratas , Xenopus laevis/embriologíaRESUMEN
Potential mechanisms of 4-bromobenzene-induced developmental toxicity were evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X, laevis embryos were exposed to 4-bromobenzene in two separate definitive concentration-response tests with and without an exogenous metabolic activation system (MAS) or selectively inhibited MAS. The MAS was treated with carbon monoxide (CO) to modulate P-450 activity, cyclohexene oxide (CHO) to modulate epoxide hydrolase activity, and diethyl maleate (DM) to modulate glutathione conjugation. Addition of the intact MAS, and particularly the CHO- and DM-inhibited MASs, dramatically increased the embryo lethal potential of 4-bromobenzene. Addition of the CO-inhibited MAS decreased the developmental toxicity of activated 4-bromobenzene to levels approximating that of the parent compound. Results from these studies suggested that a highly toxic arene oxide intermediate of 4-bromobenzene formed as the result of mixed function oxidase (MFO)-mediated metabolism may play an important role in the development toxicity of 4-bromobenzene in vitro. Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be responsible for activated 4-bromobenzene detoxification.