Inhibitory and Intensifying Effects of Long-Term Exposure to Chemicals on Spontaneous Hepatic Injury in LEC Rats

Abstract

Liver disease, including the so-called hereditary hepatitis [1–4] and subsequent hepatocellular carcinoma [5, 6], and hypoplasia of the thymus [7], are presently known as characteristic morphological abnormalities in LEC rats. Basically, the hepatic lesions of this mutant strain of rat are liver cell degeneration and necrosis, and accumulation of hepatocytes with polyploid huge nuclei [8]. The pathogenesis of hepatic injury has not yet been elucidated, but recently the possibility of the abnormality of methionine metabolism has been suggested from the results of DL-ethionine administration [9]. In examining the response to short-term administration of chemicals or to physical stimulation, the following results have been reported: (1) delay of the hepatic injury by daily intragastric administration of high doses of phenobarbital [10], (2) intensification of hepatic injury by a choline-deficient diet [11] or 0.1% DL-ethionine [9], (3) high susceptibility to initiation by diethylnitrosamine [12], and (4) inhibitory effect of a two-thirds partial hepatectomy on hepatic injury [13].