PATHOLOGICAL MECHANISMS OF HEPATIC TUMOR-FORMATION IN RATS EXPOSED CHRONICALLY TO DIETARY HEXACHLOROBENZENE

The chronic dietary administration of hexachlorobenzene (HCB) to rats for a year or more results in the formation of liver tumours described as hepatocellular carcinomas, hepatomas or haemangiomas. The hepatoto xicity of HCB, which is greatest in hamsters and rats, gives rise to p eliosis and necrosis with haemosiderosis. This pattern of hepatotoxici ty indicates vascular damage, which through haemosiderosis could incre ase not only the toxic effect of HCB to hepatocytes but also its tumou rogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chr onically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas wit h elements of peliosis (cystic blood-filled cavities) could be explain ed by the compensatory hyperplastic responses to hepatocellular necros is and by the simultaneous loss of hepatocellular cords. The accumulat ion of iron in the liver would strongly potentiate the development of hepatic tumours, as has been found in HCB and polychlorinated biphenyl -treated mice with iron overload. The implications of this non-genotox ic mechanism of hepatoma formation for the assessment of human health risk are discussed.