<Originals>Effects of partial hepatectomy, phenobarbital and buthionine sulfoximine on rat hepatocytes positive for the placental form of aflatoxin B_1-induced glutathione transferase

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概要

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• Biochemical studies have indicated that glutathione (GSH) and glutathione-S-transferases (GSTs) play an important role in modulating hepatic aflatoxin B_1 (AFB_1)-DNA binding and AFB_1 hepatocarcinogenesis in the rat. The presence of GST-placental (GST-P) form positive hepatocytes is considered to be an early marker for initiation during the hepatocarcinogenesis. The effects of partial hepatectomy, phenobarbital (PB) and buthionine sulfoximine (BSO) pretreatments of rats have been examined on AFB_1-induced GST-P positive single hepatocytes using a single dose carcinogen model. Young male Fischer rats fed a commericial diet with or without 0.1% PB in their drinking water for 1 wk were used for these studies. Some rats were partially hepatectomized 18-20 hr before AFB_1 administration whereas some rats were injected with 4 mmol BSO/kg body wt 4 hr and 2 hr before intraperitoneal (i.p.) injection of AFB_1. Most animals were injected i.p. with AFB_1 whereas some animals were injected i.p. with DMSO alone. Livers of all rats sacrificed 48 hr or 144 hr after DMSO or AFB_1 treatment were fixed for immunohistochemical demonstration of GST-P positive hepatocytes. Partial hepatectomy before AFB_1 (0.5-4.0 mg/kg body wt) injection yielded 2-3 times as many GST-P positive single hepatocytes/sq.cm. as sham operated rats 48 hr after AFB_1 injection. Control, PB- or BSO-pretreated rats without AFB_1 injection produced a small number of about 0.3/sq. cm. GST-P positive hepatocytes whereas control and PB-treated rats after AFB_1 (2 mg/kg body wt) treatment yielded about 10.1 and 2.8 GST-P positive hepatocytes/sq. cm. respectively. Pretreatment of these two groups with BSO before AFB_1 injection increased the yield of GST-P positive hepatocytes by 145% and 180% above their respective controls. Similar data were obtained when rats were sacrificed 144 hr after AFB_1 injection. In these studies, all rats pretreated with BSO died within 144 hr after AFB_1 injection. Pretreatment with PB inhibited AFB_1-induced GST-P positive hepatocytes by 90% control levels. Pretreatment with BSO of PB-treated rats increased the yield of AFB_1-induced GST-P positive hepatocytes by 580% PB-controls. A small number of AFB_1-induced GST-P positive minifoci (6-8) was also observed with PB and BSO pretreatment of rats. The overall data suggest that PB pretreatment of rats inhibits AFB_1-induced GST-P positive hepatocytes whereas BSO pretreatment of both control and PB-treated animals enhances AFB_1-induced GST-P positive hepatocytes. These results are in agreement with previous data indicating inhibition of hepatic AFB_1-DNA binding by PB treatment and increase of AFB_1-DNA binding by BSO pretreatment of rats. Thus, there appears to be positive correlation between hepatic AFB_1-DNA binding and AFB_1-induced GST-P positive hepatocytes. The present data strongly suggest that BSO pretreatment of rats may enhance AFB_1 hepatocarcinogenesis in the rat.

• 近畿大学の論文

著者

• Horiuchi Atsushi

  Third Department Of Internal Medicine Kinki University School Of Medicine

• Tsuji Kojiro

  Third Department Of Internai Medicine Kinki University Sohool Of Medicine : Fels Institute For Cance

• LOTLIKAR Prabhakar

  Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine

• Horiuchi Atsushi

  Third Department Of Internai Medicine Kinki University Sohool Of Medicine

• Lotlikar Prabhakar

  Fels Institute For Cancer Research And Molecular Biology Temple University School Of Medicine

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