Modification of the immune response by organochlorine xenobiotics.
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Biomedical subjects
Publications and source records attributed to K F Benitz.
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Antibody formation, endotoxin sensitivity, and resistance to a challenge malarial infection were evaluated in mice fed a diet containing polychlorinated biphenyl (PCB) (Aroclor 1242) or hexachlorobenzene (HCB). Antibody synthesis to the antigen sheep RBC (SRBC) was significantly depressed in the PCB- and HCB-treated (167 ppm) animals as evidenced by the fact that control mice elicited an approximate twofold increase in antibody formation over the chemical-treated mice. Serum IgA concentrations in the PCB- and HCB-treated mice were consistently 40--80 mg/dl lower than control values. Gram-negative endotoxin (Salmonella typhosa) sensitivity in PCB- and HCB-treated mice was increased 5.2- and 32-fold, respectively, following the dietary administration of 167 ppm of Aroclor 1242 or HCB for 6 weeks. An endotoxin hypersusceptibility was also noted at 3 weeks after dietary administration. Decreased resistance to a malaria challenge was also demonstrated in the xenobiotic-treated mice. A 20% decrease in mean survival time of mice fed Aroclor 1242 for 3 to 6 weeks and inoculated with Plasmodium berghei (NYU-2) was observed. Infected mice which had received HCB for 3 or 6 weeks manifested reductions in mean survival time of 24 and 31%, respectively. The data indicated that environmental chemical contaminants impair host resistance and, since no concomitant histopathological alterations were observed in the treated mice, the evaluation of immune parameters may possibly be a sensitive indicator of toxicity.
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The in vivo effect of polychlorinated biphenyl (PCB) and hexachlorobenzene (HCB) on murine endotoxin sensitivity and resistance to malaria (Plasmodium berghei NYU-2) infection was studied. The dietary administration of 167 ppm (167 microgram/g) of PCB 1242 or HCB for 3 weeks resulted in an enhanced sensitivity to gram-negative endotoxin (Salmonella typhosa), which was further increased in animals maintained on the diets for 6 weeks. By 6 weeks, a 5.2- or 32-fold increase in endotoxin sensitivity was seen in mice fed PCB or HCB, respectively. A 20% decrease in mean survival time of mice fed PCB 1242 for 3 or 6 weeks and inoculated with malaria was demonstrated. Infected mice that received HCB for 3 or 6 weeks manifested a reduction in mean survival time of 24 or 31%, respectively. Histopathological examination revealed a normal thymus, spleen, mesenteric lymph nodes, and lungs. Centrilobular and pericentral hepatocyte hypertrophy, common to organochlorine exposure, was observed. Electron capture gas chromatographic analysis for PCB 1242 or HCB in the tissues examined histologically revealed a significant deposit of the xenobiotics. HCB concentration was approximately 16 to 25 times greater than that of PCB. The data indicate that environmental chemicals impair host resistance and that the alteration may be related to the presence of the chemicals in the lymphoreticular organs.
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The surface epithelium and stromal elements in the ovary of the rhesus monkey were studied with a variety of fluorescence-histochemical procedures to determine the relative distribution of specific chemical moieties. The surface (germinal) epithelium displayed high levels of cytoplasmic RNA and specifically intense fluorescence with methods that demonstrate basic, SH and SS groups of protein. The underlying basement membrane demonstrated an intense reaction when fluorochromed with hydroxynaphthoic acid hydrazide directed toward side-chain carboxyl groups of protein. The fluorescence pattern displayed by the underlying connective tissue was heterogeneous and related to its anatomical localization. It is suggested that this heterogeneity reflects specific, but as yet undefined, chemical differences in the fibrous elements of the ovary.