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

被引:14
作者
CARTHEW, P
SMITH, AG
机构
[1] MRC Toxicology Unit, University of Leicester, Leicester, LE1 9HN, Hodgkin Building, PO Box 138, Lancaster Rd
关键词
LIVER; TUMOR; HEXACHLOROBENZENE; FIBRIN; VASCULAR; TOXICITY; RAT; HYPERPLASIA; HEMOSIDEROSIS;
D O I
10.1002/jat.2550140610
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 hepatotoxicity of HCB, which is greatest in hamsters and rats, gives rise to peliosis and necrosis with haemosiderosis. This pattern of hepatotoxicity indicates vascular damage, which through haemosiderosis could increase not only the toxic effect of HCB to hepatocytes but also its tumourogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chronically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas with elements of peliosis (cystic blood-filled cavities) could be explained by the compensatory hyperplastic responses to hepatocellular necrosis and by the simultaneous loss of hepatocellular cords. The accumulation 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-genotoxic mechanism of hepatoma formation for the assessment of human health risk are discussed.
引用
收藏
页码:447 / 452
页数:6
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