Chronic liver injury promotes hepatocarcinogenesis of the LEC rat

Abstract

The Long-Evans rat with a cinnamon-like color (LEC) is a mutant rat that spontaneously suffers from chronic liver injury and subsequent hepatocellular carcinoma (HCC) caused by abnormal copper accumulation in the liver. We attempted to elucidate the role of prolonged liver cell injury on LEC rat hepatocarcinogenesis using a copper-deficient diet (CuDD) to inhibit the occurrence of consequent liver injury. The animals were fed the CuDD from the age of 4 weeks until being killed at the age of 10 months. Diethylnitrosamine (DEN) was administered at the age of 8 weeks. Groups fed a basal diet (BD) with or without the administration of DEN were also assigned as control groups. The animals fed the BD manifested liver injury, while those fed the CuDD did not show liver dysfunction until death. The number and volume of glutathione S-transferase placental form (GST-P)-positive preneoplastic lesions in the liver, which were calculated from the data on two-dimensional planes, were examined to clarify the promotive effect of chronic liver injury on the development of HCC. Regarding the size of the lesions, which indicated the intensity of the promotive effect, the lesions in the livers of rats fed the BD with DEN were much larger than those of rats fed the CuDD with DEN. Feeding the LEC rats with CuDD completely suppressed the manifestation of liver injury, and it was clearly shown that prolonged liver injury had a promotive effect on the LEC rat hepatocarcinogenic process.

Water extracts of cabbage and kale inhibit ex vivo H2O2-induced DNA damage but not rat hepatocarcinogenesis

“…However, in our experiment, treatment with CB or K extract did not inhibit or increase the number or aggregated area of GST-P-positive hepatic PNL. The size of GST-P PNL in rats is generally considered to be a reflection of the magnitude of hepatocarcinogenesis promotion, and their number is related to the intensity of the initiation process (30). Thus, under our experimental conditions these Brassica vegetables did not present chemopreventive or initiating or promoting effects at a stage that can be considered to be very early promotion, since GST-P-positive PNL were of very small size.…”

A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats

“…Copper and iron ions produce oxygen radicals that cause cell damage (Sone et al, 1996;Kato et al, 1996). One-third of LEC rats die of acute hepatitis with submassive or massive necrosis of hepatocytes at approximately four months of age (Kato et al, 1996;Sawaki et al, 1998).…”

Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue

“…GST-pi is an acid GST, isolated and purified from human term placenta, which possesses catalytic and ligand-binding properties, and is regarded as a new marker enzyme for tumors. Some studies reported that GST-pi or GST-pi mRNA is hardly detectable in normal liver, but markedly increases in preneoplastic hepatic lesions such as hyperplastic nodules and in HCC by immunohistochemical staining or in situ hybridization [13][14][15][16] , suggesting that GST-pi is a sensitive marker enzyme for preneoplastic lesions and neoplastic cells, not only at the protein level but also at the mRNA level, throughout the hepatocarcinogenesis in rat liver. In addition, other studies reported that single cells immunohistochemically positive for GST-pi induced in the rat liver carcinogenesis by chemical carcinogens are precursor-initiated cells of preneoplastic foci, GST-pi content in the single cells is higher than that in preneoplastic foci, and GST-pi is a more sensitive marker for detection of HCC than γ-GT or AFP [17][18][19][20] .…”