Failure of glutathione to prevent liver cancer development in rats initiated with diethylnitrosamine in the resistant hepatocyte model

Abstract

This study was undertaken to observe whether the administration of reduced glutathione intragastrically to male Fischer 344 rats during the precancerous steps of liver carcinogenesis has any protective effect on the development of hepatocellular carcinoma. Hepatocyte nodules were induced in the liver with a single initiating dose of diethylnitrosamine followed by selection of resistant hepatocytes to generate nodules by a two week exposure to dietary 2-acetylaminofluorene coupled with partial hepatectomy. Animals had hepatocyte ('hyperplastic') nodules when examined by laparotomy at three months. At that time, the animals were divided into two groups. One received daily intragastric glutathione for 8 months while the other received no further treatment. An additional control group received only the selecting (promoting) regimen with no initiator or glutathione. At 12 months, the animals receiving the initiator and promoter regimen had a 65% incidence of hepatocellular carcinoma and those receiving glutathione in addition had a 71% incidence. Under these experimental conditions, the long term administration of glutathione appears to have no observable influence on liver cancer development in this model.