Alterations in guinea pig hepatocytes exposed to chlorinated hydrocarbons: membrane proliferation and excretion.

Polychlorinated aromatic hydrocarbons are a widespread, extremely toxic group of environmental pollutants. A fine soot containing a mixture of these compounds contaminated an office building after a fire involving an electric service transformer and its polychlorinated biphenyl (PCB) containing cooling fluid. The soot was found to contain polychlorinated dibenzo-p-dioxins (PCDD), and dibenzofurans (PCDF). Guinea pigs fed this soot develop steatosis and smooth endoplasmic reticulum (SER) proliferation as major hepatocyte alterations. The proliferated SER is associated with cytoplasmic vacuoles and laminated concentric membrane arrays (CMAs) usually associated with lipid. High-voltage electron microscopy examination of serial 0.25 micron sections revealed an occasional vacuole communicating directly with either a sinusoid or bile canaliculus. This channel provided a pathway for the ejection of membrane sheets and condensed fragments which shed from the luminal surface of the vacuoles. In addition, membrane sheets from the CMAs and proliferated SER were also ejected into the vacuoles. This resulted in continuity from the hepatocyte cytoplasm to the sinusoids and bile canaliculi via the vacuoles. Membrane sheets were also shed directly from the luminal surface of the bile canaliculi. Numerous membrane sheets and condensed fragments were found in the sinusoids, bile canaliculi and ducts. These morphologic observations elaborate a mechanism of direct and indirect membrane ejection from the hepatocyte into the blood and bile spaces and may explain the origin of reported elevated serum bilirubin and cholesterol levels. Since these PCDDs and PCDFs are excreted primarily via the bile, this ejection mechanism may be important in the detoxification process.