Wirkung einer zweiten CCl4- Intoxikation auf die CCl4-geschädigte Leber der Maus

Abstract

The effect of a second CCl4 intoxication on the CCl4-pretreated mouse liver is investigated. After a single dose of 1 ml/kg CCl4 injected intraperitoneally all CCl4-sensitive hepatocytes are destroyed. These CCl4-sensitive cells, localized in the centrolobular area, represent 55% of the total liver volume. During the 10 day period of regeneration the liver parenchyma is completely resistant to any further CCl4 intoxication, even at doses 3–5 fold lethal to normal mice. Shortly after regeneration is completed the liver regains its CCl4 sensitivity. As in the single CCl4 intoxication cell damage is confined to the centrolobular area and is characterized by a breakdown of protein synthesis and a subsequent necrosis. Time course and extent of the damage are completely identical with that after a single CCl4 intoxication. Continuous infusion of3H-thymidine leads to a 100% labeling of the CCl4-undamaged peripheral liver cells 4 days after a single CCl4-injection. Only part of these S-phases is necessary for the replacement of necrotic cells by normal mitoses. The larger part of the S-phases results in nuclei of higher ploidy stages. Considering both processes, mitosis and polyploidization, as a formation of new cells, the liver after regeneration from CCl4 intoxication must be regarded as consisting completely of new cells. By the end of regeneration the liver consists only of CCl4-resistent cells. The sensitivity to CCl4 regained in the centrolobular region after regeneration demonstrates that the genetic information for induction of enzymes capable of toxic conversion of CCl4 must also exist in peripheral liver cells and their descendants. However, this information is only activated in centrolobular liver cells, i.e. its activation depends on the localization of the cell within the lobule.