Amino acid metabolism of different mammalian cell lines.
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Biomedical subjects
Publications and source records attributed to R A Chung.
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Rabbits were administered DDT (10 mgQ/kg) and rabbits and goats were administered pure PCB compounds or PCB mixtures (25 mg/kg for rabbits and 5, 10 or 20 mg/kg for goats). All rabbits were also injected with ovalbumin and goats with Salmonella enteritidis-O antigen. Animals were sacrificed on day 21 when maximum antibody titer was obtained. Rabbits treated with 20 mg/kg DDT showed significantly reduced weight gain, feed consumption, weights of lung, liver and spleen, antiovalbumin synthesis in lung and spleen and maximum serum antibody titer. In addition, in the liver, protein, DNA and RNA contents and aminoacyl t-RNA activity were reduced. A decrease in serum protein was reflected in a decrease in albumin and gamma- and beta-globulin. Pure PCBs or PCB mixtures did not affect body weight, feed consumption or organ weights of rabbits. Protein and/or antiovalbumin synthesis increased in kidney, spleen and lung in rabbits after treatment with Aroclor 1242 or Aroclor 1254. PCB compounds decreased body weights but did not affect organ weights of goats except for a liver weight increase at 20 mg/kg for 2,4-DCBP, Aroclor 1268 and PCT. Aroclors 1242, 1254 and 1268 significantly decreased anti-Salmonella enteritidis synthesis in lymph node, spleen and bone marrow in goats at 20 mg/kg. However, at 5 mg/kg, a significant increase in antibody synthesis was observed. Ultrastructural evaluation of PCB-treated rabbits revealed little or no pathological change at these dose levels.
In vitro administration of DDT at 0.5 ppm, 10 ppm, and 50 ppm (0.5, 10 and 50 micrograms/ml culture medium) to HeLa S, human amnion (HA-FL), canine venereal tumor (CVT), canine kidney (MD-CK) and rat nephroma (RN) cells resulted in alterations of the ultrastructure of cells. Responses to the cytotoxic chemical compound were qualitatively and quantitatively similar among all mammalian cell lines tested. The tested cells exhibited dose-specific responses. Al low dose (0.5 ppm) rough endoplasmic reticulum and free ribosomes increased as did the number and size of smooth endoplasmic reticulum profiles. At higher doses (10 ppm and 50 ppm) there was indication of cellular degradation including mitochondrial disorganization, nuclear heterochromatic condensation and peripheralization, and increases in numbers of lysosomes, autophagic vacuoles and multivesicular bodies. This suggests that low level exposure to cytotoxic elements such as DDT initiates a repair and regeneration response from the cells while degenerative changes at higher exposure levels suggest less success with detoxification and possible irreversible cellular damage.
Three agriculturally important minor species, the goat, rabbit, and duck, were exposed to various subclinical levels of pure polychlorinated biphenyls (PCBs) and/or PCB mixtures (Aroclors) for short periods of time. Upon sacrifice, liver samples were prepared for ultrastructural observation. Regardless of species, hepatocytes displayed qualitatively similar morphological responses to PCB exposure. At lower exposure levels, cellular changes included increased density of mitochondrial matrix and proliferation of endoplasmic reticulum. At higher exposure levels, degradative changes such as cytoplasmic loss and peripheralization of cytoplasm and organelles became more obvious. When compared quantitatively, it was obvious that goats were much more sensitive to PCB exposure than either rabbits or ducks. Goats showed extensive hepatocyte degradation (cytoplasmic and nucleoplasmic leaching) at exposures of 2 mg/kg body weight of Aroclor 1254. Such species-related differences in response to chlorinated biphenyls cautions against the use of single species animal models in xenobiotic exposure studies.