Sublethal effects of a pure polychlorobiphenyl on mice

Sexually mature, weight-stable male mice were dosed by oral intubation with either 0, 200, 500, or 1000 mgm/kgm of 2,4,5,2′,4′,5′-hexachlorobiphenyl (PCB), dissolved in peanut oil, and housed for 28 days in groups of five in metabolic cages. Their food and water consumption, urine and fecal (dry) output, and body weights were not depressed or enhanced by the PCB treatment; nor were any neuromuscular deficiencies detected by rotarod tests. At the termination of the experiment, hematocrit values were not significantly changed. The wet weights (percentage of body weight) of whole brain, testes, and epididymal fat pads were not changed significantly in the PCB-treated animals. However, wet spleen weights of those animals receiving 500 mgm of PCB/kgm were significantly depressed and the wet kidney weights of animals receiving 500 and 1000 mgm of PCB/kgm were also decreased significantly. The wet and dry weights of livers were significantly elevated in animals treated with 500 and 1000 mgm of PCB/kgm. The average amount of PCB extracted from dry livers increased significantly with each higher dose of PCB administered. Linear regression analysis revealed a dose-related response in the amount of PCB sequestered in the liver. The polychlorinated biphenyl extracted from dry livers was confirmed, by mass spectral analysis, to be 2,4,5,2′,4′,5′-hexachlorobiphenyl. Concerning cytologic changes in hepatocytes, the mean cell volume, mean nuclear volume, and mean cytoplasmic volume of centrilobular hepatocytes treated with 200 mgm of PCB/kgm (and higher) were all significantly greater than these same parameters in the centrilobular hepatocytes of untreated animals. No cytologic volume changes were detected in the periportal hepatocytes. Morphometric analysis of electron micrographs (35,000x) from each of 11 mice (three mice given 200 mgm of PCB/kgm and four mice each given 0 or 1000 mgm of PCB/kgm) revealed that the number of lipid bodies and mitochondria per cell were significantly higher in the average centrilobular hepatocyte treated with 1000 mgm of PCB/kgm. The membrane surface areas (expressed as square microns) were also significantly elevated in the mitochondrial envelope, the mitochondrial cristae, and the smooth endoplasmic reticulum per centrilobular hepatocyte. The volumes (expressed as cubic microns) of numerous cytoplasmic components were significantly greater in the centrilobular hepatocytes treated with 1000 mgm of PCB/kgm; these include lipid bodies, secondary lysosomes, mitochondria, rough and smooth endoplasmic reticulum, and open cytoplasm. In conclusion, this study gives a detailed quantitative morphometric description of the way in which centrilobular hepatocytes adapt to the toxic effects of a persistent environmental contaminate, 2,4,5,2′,4′,5′-hexachlorobiphenyl.