Bromobenzene-induced zonal necrosis in the hepatic acinus.

The time course and acinar distribution of bromobenzene-induced hepatic necrosis was studied in the rat. Cellular damage, lipid infiltration, and changes in glycogen deposits were investigated by light microscopy 6, 16, 24, and 48 hr after bromobenzene (BZ) administration. Concomitantly, ultrastructural changes were followed by electron microscopy in each zone of the acinus. To insure accurate orientation in acinar zones, a double embedding technique for electron microscopy was used. Acinar zones were localized by light microscopy and subsequently re-embedded for electron microscopy. Zone 3 was the site of conformational changes in smooth endoplasmic reticulum 6 hr after BZ administration. This condensed, tubular network represented the earliest morphological sign of injury observed by electron microscopy. At 48 hr, cytoplasmic vacuolar degeneration and necrosis were observed in the hepatocytes of acinar zone 3. While no necrosis was observed in the cells of zone 1, other morphological changes occurred. These included progressive lipid accumulation, as well as fluctuations in the amount of rough endoplasmic reticulum and free ribosomes. These latter observations suggested a possible link between protein manufacture and survival of the zone 1 cells. These results established that, following bromobenzene administration, necrosis was restricted to zone 3 hepatocytes.