The effect of adult exposure to diethylstilbestrol in the mouse: alterations in tumor susceptibility and host resistance parameters.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M I Luster.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of TCDD exposure on the developing immune system were investigated in Wistar/Fischer hybrid or Fischer rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 muk/kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats was exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group 2). Variable but significant effects on body weights and thymus/body weight ratios were found up to 133 days of age. Cell mediated immune functions were depressed up to 133 days of age in both groups but less severely in animals exposed only postnatally. Furthermore, TCDD suppressed cell-mediated immune functions without affecting humoral immune function. Adoptive cell transfer studies indicated suppression of T-cell functions was selective in that "helper" cell function was not suppressed. In other studies, the effects on lymphocyte function following brief exposure of spleens from B6C3F1 mice to TCDD in dimethylsulfoxide (DMSO) were investigated. DNA, RNA and protein synthesis were inhibited at concentrations less than 2 X 10(-7) M TCDD in DMSO. This concentration accounted for approximately 0.2 ng TCDD uptake per spleen. The structurally related chemicals 3,4,3',4'-tetrachlorobiphenyl and 1-amino, 3,7,8-trichlorodibenzop-p-dioxin did not show significant lymphocyte effects even at two-fold higher concentrations. The ability of lymphocyte mitogens to bind to their cell surface receptors was not affected by TCDD treatment. TCDD was slightly cytolytic to lymphocytes after 48 hours of culture. DMSO treatment alone was also slightly toxic to lymphoid cells as indicated by a 10--20% loss of cell viability, although this occurred within 4 hours after DMSO exposure. Studies were performed to investigate the effects of 2,3,7,8-tetrachlorodibenzofuran (TCDF) on immune function in adult Hartley guinea pigs. Animals received 6 weekly doses of either 0, 0.05, 0.17, 0.5 or 1.0 microgram TCDF/kg body weight. TCDF slightly depressed cell-mediated immune functions, particularly at the higher dose levels as indicated by decreased lymphocyte blastogenesis, delayed hypersensitivity reactions, and production of macrophage inhibitor factor. Additionally, thymus-to-body-weight ratios were slightly reduced in the 0.5 and 1.0 microgram dosage groups. Serum IgG levels and antibody titer to BGG did not differ from controls. These results indicate that TCDF-induced immunosuppression is similar to that of TCDD.
The effects of TCDD exposure on parameters of immune function during the developmental period were investigated. Exposures were performed in Fischer/Wistar rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 micrograms/Kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats were exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group 2). Body weights and relative thymus weights were found to be suppressed up to 135 days of age in group 1 but only up to 35 days of age in group 2. Parameters of cell-mediated and humoral immune function were investigated. TCDD suppressed cell-mediated immune function without affecting humoral immune function. TCDD-exposed animals had recovered normal cell-mediated immune function by 270 days of age. A group of inbred Fischer rats was exposed to TCDD as described for group 1 above. At 45 days of age these animals were utilized in lymphocyte homing studies. It was found that TCDD exposure alters homing patterns of lymphocytes from exposed animals when adoptively transferred to untreated animals. In addition, lymphocytes from nonexposed animals did not home normally when injected into TCDD-exposed recipients.
The rational for employing a particular approach and some of the difficulties that can be encountered when adapting immune surveillance to toxicology studies in experimental animals are discussed. Detailed description of methodology will not be reviewed. In general, assays are selected for their reliability, i.e. fairly standard within a normal population; that are capable of detecting subtle differences in immune status; and are specific for particular aspects of the immune system. Since normal immune responses are directly dependent upon at least three distinct subpopulations of lymphocytes, macrophages and their cooperative interactions as well as a number of indirect factors, it is essential to study multiple parameters to properly evaluate the effects of environmental chemicals on the immune system. Immunologic assessment is further complicated by the fact that the immune effects will vary dependent upon the chemical and dosage level as well as the species and age of the experimental animals.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects of TCDF exposure on the immune system were investigated in Hartley guinea pigs. TCDF was administered by gavage at doses of 0.05, 0.17, 0.5 or 1.0 microgram/kg body weight once weekly for six weeks. Thymus/body weight ratios were suppressed in the higher dosage groups. Parameters of cell-mediated and humoral immune function were investigated. TCDF modestly suppressed cell-mediated immune function and had slight effects on humoral-mediated functions. TCDF immunosuppression appears similar to that induced following exposure to TCDD.
Studies were performed to investigate the effects of chronic, low level pre- and post-natal lead exposure on cell-mediated immune function in rats. Weanling female rats were exposed to lead (as lead acetate) in their drinking water at 0, 25, and 50 ppm for 7 weeks. At the end of 7 weeks they were mated with untreated males and continued on the same dosage throughout gestation and lactation. The offspring of these females were weaned at 21 days of age and continued on the same lead exposure regimen as their mothers. These offspring were used in immune surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to mitogen stimulation and in reduced delayed hypersensitivity responsiveness. Results indicate that chronic low-level lead exposure causes suppression of cell-mediated immune function.
The antibody response to SRBC and E. coli 0127 lipopolysaccharide were determined in offspring from mice exposed in utero to diethylstilbestrol. The antibody response to SRBC, a T-cell dependent antigen, was similar in control and exposed animals. In contrast, the LPS antibody response was suppressed in treated females and enhanced in treated males. These studies indicated that in utero exposure to DES alters the humoral immune system to T-independent antigens.
Explore the source record for details and available documents.
Sera and cerebrospinal fluids (CSF) from patients with subacute sclerosing panencephalitis (SSPE) were tested by indirect immunofluorescence for the presence of measles virus specific antibodies of the various heavy chain classes. IgG and IgA antibodies were detected in the CSF while IgG, IgM, IgA, IgD and IgE measles virus antibodies were found in a significant number of the patient sera. Sera from SSPE patients had slightly elevated levels of IgG, IgM, IgD and IgE while IgA was decreased. The heterogeneous heavy chain class distribution of measles antibodies suggests the possibility that non-complement fixing antibodies serve as blocking antibodies which aid in the persistence of intracellular measles virus infection in patients with SSPE.
Studies were performed to investigate the effects of FireMaster FF-1, a chemical fire retardant consisting of a mixture of polybrominated biphenyls (PBB), on immune functions in mice and rats. Animals received 22 daily treatments of 0.03, 0.3, 3.0, or 30 mg PBB/kg body weight in a period covering 30 days. PBB exposure severely depressed cell mediated immunity in both mice and rats at the higher dosage levels as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Additionally, humoral immunity was depressed in mice at the 30.0 ppm dosage level. Assays for humoral immune functions included antibody production, serum immunoglobulin levels, and mitogenic stimulation of splenic lymphocytes to a polyclonal B-cell activator. These studies indicate that PBB exposure can lead to suppression of both humoral and particularly cell-mediated immune responses.
We report a radioimmunoassay for mono-(2-ethylhexyl) phthalate that has been coupled to a protein carrier as a radioligand. Competitive interference tests with a variety of related compounds indicated the assay to be highly specific. Quantitative comparison of mono-(2-ethylhexyl) phthalate values in plasma and serum samples between the radioimmunoassay and gas chromatographic procedures indicated a high reliability. Because this potentially toxic compound can leach into plasma from polyvinyl plastics, this assay should be particularly useful for those involved in the manufacture or use of medical devices made of them.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.