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Biomedical subjects

J H Exon

Publications and source records attributed to J H Exon.

At least 55 records · Page 3Linked to original sources

The immunotoxicity of selected environmental chemicals, pesticides and heavy metals.

It is an established fact that certain environmental chemicals, pesticides and heavy metals can alter the immune response of laboratory animals and probably humans as well. In some instances, the immune system appears to be exquisitely sensitive to these agents compared to other toxicologic parameters. Both stimulation and suppression of immune responses have demonstrated in contaminant-exposed animals. Although the majority of data accumulated to date pertains to effects in small laboratory rodents, there is little reason to believe that similar quantifiable effects do not occur in domestic and food-producing animals due to basic functional similarities of the immune system of mammals in general.

Animals↗

Comparison of selenium levels and glutathione peroxidase activity in bovine whole blood.

Blood glutathione peroxidase activity and selenium levels were found to correlate well, indicating that glutathione peroxidase activity can be used to assess blood selenium levels in beef cattle. The glutathione peroxidase activity of blood is less stable than is the selenium concentration but when blood was stored at 4 degrees C, the glutathione peroxidase activity remained constant for seven days.

Animals↗

Effects of chlorinated phenols on immunity in rats.

Female Sprague - Dawley rats were exposed to 0, 5, 50 or 500 ppm 2-chlorophenol (2-CP) or pentachlorophenol (PCP) from weaning to 3 weeks postparturition after breeding at 90 days of age. Progeny were weaned at 3 weeks of age and continued on chlorophenol treatment for 10 weeks at which time major immune functions were tested. Humoral immunity was measured by an indirect ELISA, cell-mediated immunity was monitored by delayed-type hypersensitivity (DTH) to oxazolone, and macrophage function was tested by phagocytosis of sheep red blood cells. Rats treated with cyclophosphamide were included as a positive immunosuppressed control. PCP-treated rats had significantly decreased antibody titers and DTH response and increased induced peritoneal macrophage numbers which displayed hyperphagocytic activity. Immune responses in rats treated with 2-CP were not significantly different from controls. The data indicate that (1) the immune system may be a sensitive target for PCP toxicity but not for 2-CP, (2) closely related chlorophenolic chemical isomers may exert different toxic effects on the immune system, and (3) PCP can exert depressive effects on some major immune parameters while enhancing others.

Animals↗

Evaluation of ELISA for detecting in vivo chemical immunomodulation.

Immunotoxicology is a relatively new field of investigation and is becoming recognized and used by toxicologists involved in drug and chemical testing. The purpose of this study was to evaluate the enzyme-linked immunosorbent assay (ELISA) as a means of quantitating humoral immune responses in rats exposed to immunomodulating chemicals. The ELISA proved to be highly sensitive and quantitative, simple to perform, and reliable. The assay is also economically feasible and automated so that large numbers of samples can be analyzed at one time. The antigen used in the study was bovine serum albumin, and the immunosuppressive chemicals used to validate the system were lead, polychlorinated biphenyl, cyclophosphamide, and dexamethasone. Practical application of the procedure to immunotoxicology testing is discussed.

Animals↗

Selenium deficiency of beef cattle in Idaho and Washington and a practical means of prevention.

The majority of beef cattle assayed for whole blood glutathione peroxidase (GSH-Px) activity in Idaho and Washington were deficient in selenium. Cattle in the more arid sections of these states tended to have higher selenium levels than those in areas with moderate and high rainfall. Animals pastured on irrigated forages had lower selenium concentrations than those grazed on dry land pasture. Cattle were supplemented by the addition of sodium selenite to a salt-mineral mixture. Ninety mg selenium per kg (ppm) salt-mineral mix fed to cattle significantly (P less than 0.001) elevated selenium (GSH-Px) levels well into normal ranges by 3 months when fed to extremely selenium deficient animals. Thirty ppm selenium was insufficient to raise GSH-Px levels into normal ranges. In addition, 20 ppm selenium was insufficient to sustain blood selenium concentrations of selenium adequate animals. Selenium given in the salt-mineral mix provided an effective, economical, and easily regulated source of dietary selenium. This supplement can be provided the entire year even under range conditions. Calves of cows placed on the 90 ppm selenium supplement had significantly (P less than 0.005) improved weaning weights (10 months) and an indication of a decreased incidence of infectious diseases.

Animals↗

Influence of diet on the effects of selenium in the genesis of mammary tumors.

Two experiments were conducted to study the interaction of various diets with selenium in the genesis of mammary tumors. In the first experiment, virgin C3H mice were fed either an Oregon State University (O.S.U.) chow or this chow plus 0.5 or 2.0 ppm selenium in the drinking water, or Wayne Lab-Blox Chow with or without 2.0 ppm selenium in the water. Selenium significantly reduced the tumor incidence in mice fed the O.S.U. chow, but not in those fed the Wayne chow. In the second experiment, virgin female C3H mice were fed a purified casein-based diet with either lard, butter, corn oil, or rapeseed oil at a 10% level without or with selenium (2 ppm) in the drinking water. Selenium had no significant effect upon tumor incidence in this experiment. Thus, these results indicate that the type of diet has a marked influence on the beneficial effects of selenium in reducing mammary tumors in C3H mice.

Animals↗

Effects of transplacental exposure to chlorinated phenols.

Female rats were exposed to 0, 5, 50 or 500 ppm of 2-chlorophenol (2-CP) or pentachlorophenol (PCP). The study was designed to produce progeny which were exposed to the chlorophenolic compounds both prenatally and postnatally. Percent conception, litter size, birth weight, and number of stillbirths was determined at parturition. Hematologic parameters and body weights of the progeny were recorded at weaning age (3 weeks). Effects on reproduction were observed in both the 2-CP and PCP-exposed groups, as indicated by decreased litter sizes and increased number of stillborn. The data indicate that these chlorinated phenolic compounds may be feto- or embryotoxic at high doses. Effects on hematologic parameters were not observed. Further study involving transplacental and chronic exposures to these chlorophenolic compounds appears warranted.

Animals↗

Immunotoxicology studies of sodium arsenate-effects of exposure on tumor growth and cell-mediated tumor immunity.

Exposure of mice to sodium arsenate (Na2HAs04) at levels of 2.5, 25 and 100 ppm As in the drinking water for 10-12 weeks increased the latent period and decreased the incidence of tumors induced by injection of MSB sarcoma cells. Tumor growth and regression induced by Moloney sarcoma virus (MSV) was not significantly affected by arsenic exposure. Cell mediated tumor immunity was either unaffected or enhanced by exposure to arsenic. Our results indicate that chronic exposure to sodium arsenate at arsenic levels as high as 100 ppm is not detrimental to mice in terms of tumor growth and immunosuppression.

Animals↗

Methylmercury: effect on serum enzymes and humoral antibody.

Dosages of 20 and 10 ppm methylmercury were toxic to rabbits while 1 ppm did not produce clinical signs or death. Serum alkaline phosphatase levels were elevated in all rabbits exposed to methylmercury. Methylmercury-exposed rabbits challenged to A/PR8 influenza virus had hemagglutination inhibition titers as much as four times lower than those of controls. Histopathologic lesions were found in the cerebellum of rabbits that died. The most significant features of this study were that methylmercury chloride suppressed the humoral immune system and resulted in increased serum alkaline phosphatase levels, which may aid in diagnosis when methylmercury poisoning is suspected.

Alkaline Phosphatase↗

Immune response in aged mice exposed to lead.

Mice were exposed to 0, 13, or 1,300 ppm lead in drinking water for 18 months. The immunological assays examined were mitogen (lipopolysaccharide E. coli, concanavalin A, and phytohemagglutinin-P) stimulation of lymphocytes; erythrocyte-antibody (EA), erythrocyte-antibody-complement (EAC), and phagocytosis of macrophages; and EAC of splenic lymphocytes. As measured by the majority of these assays, the low dosage (13 ppm) of lead tended to stimulate certain immune responses (lymphocyte mitosis, EA, and EAC) while the high dosage (1,300 pm) did not provoke an appreciable alteration. The results were interpreted by comparing data on aged mice with data on young adult mice. It was apparent from this comparison that the aged mice were naturally immunosuppressed. Therefore, the results obtained from lead-exposed mice were unpredictable.

Aging↗

Effect of dietary selenium on tumor induction by an oncogenic virus.

Mice exposed to selenium-supplemented or -deficient rations were inoculated with an oncogenic virus, Rauscher leukemia virus (RLV), Splenic lesions were not altered by dietary selenium supplementation or depletion. It is concluded that selenium does not affect neoplasia induced by RLV in mice.

Animals↗

Humoral antibody response in mice after single dose exposure to lead or cadmium.

A single dose of lead administered orally or intraperitoneally (IP) to mice stimulated formation of IgM antibody. Cadmium caused an increase in IgM antibody formation when injected ip but resulted in a slight decrease when given orally. Lead, orally or ip, significantly reduced IgG antibody but the IgG antibody response decreased only when cadmium was given orally and increased when injected ip. Since responses vary according to route of administration, experiments should be designed so that experimental exposure will simulate natural exposure in order to develop comparable data.

Administration, Oral↗

Hexamitiasis in cadmium-exposed mice.

Mortality was observed in 4- to 5-week-old Swiss Webster mice exposed to 300 or 3 ppm cadmium as cadmium chloride in the drinking water. Mice receiving 300 ppm cadium suffered 26% mortality as compared with 7% of those on the low cadmium dose. Death did not occur in control mice. Clinical signs and histopathology established Hexamita muris as the causative agent. Cadmium lesions were not observed. It is suggested that mortality due to hexamitiasis resulted from synergism between cadmium and H muris.

Animals↗