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Prevention of spontaneous hepatocellular carcinoma in long‐evans cinnamon rats with hereditary hepatitis by th administration of d‐penicillamine
Author(s) -
JongHon Kang,
Togashi Yuji,
Kasai Hiroshi,
Hosokawa Masuo,
Takeichi Noritoshi
Publication year - 1993
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840180321
Subject(s) - penicillamine , hepatocellular carcinoma , medicine , administration (probate law) , hepatitis , gastroenterology , political science , law
Acute hepatitis spontaneously develops in the Long‐Evans Cinnamon rat at the age of 4 mo, and eventually hepatocellular carcinoma develops after the chronic hepatitis that persists for over a year. Previously, abnormal copper accumulation was found in the livers of Long‐Evans Cinnamon rats from birth, and it was reported that short‐term administration of D‐penicillamine, a copper‐chelating agent, prevented acute hepatitis in Long‐Evans Cinnamon rats. In this study we investigated whether long‐term administration of D‐penicillamine could also prevent chronic hepatitis and subsequent hepatocellular carcinoma in Long‐Evans Cinnamon rats. During long‐term observation, which was continued from 11 to 70 wk after birth, no elevation of serum transaminase levels was observed in the Long‐Evans Cinnamon rats treated with D‐penicillamine Moreover, no histological changes characteristic of the chronic hepatitis were observed in D‐penicillamine–treated Long‐Evans Cinnamon rats, which were killed at 70 wk of age. Furthermore, placental glutathione S‐transferase–positive foci, described as a marker for preneoplastic lesions in the liver, were not detected, and thus hepatocarcinogenesis was completely prevented in D‐penicillamine–treated Long‐Evans Cinnamon rats. We also found that the amount of 8‐hydroxy‐deoxyguanosine, one of oxidative DNA damage products in the liver, was decreased in the Long‐Evans Cinnamon rats treated with D‐penicillamine. These findings suggest that a process of the prolonged liver‐cell injury and regeneration was essential for spontaneous development of hepatocellular carcinoma in Long‐Evans Cinnamon rats with abnormal copper metabolism. (HEPATOLOGY 1993;18:614–620.)