Promoting Effects of Streptozotocin-induced Diabetes on Induction of Hepatic Preneoplastic Lesions by Diethylnitrosamine in Rats

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  • Ichikawa Kazuhito
    Drug Safety Management Department, Sanwa Kagaku Kenkyusho Co., Ltd. Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical School
  • Tagawa Yoshiaki
    Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd.
  • Kawai Masaomi
    Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd.
  • Asamoto Makoto
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical School
  • Shirai Tomoyuki
    Department of Experimental Pathology and Tumor Biology, Nagoya City University Medical School

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The effects of streptozotocin (STZ)-induced diabetes on induction of hepatic preneoplastic lesions by diethylnitrosamine (DEN) were investigated in male Fischer rats. A single dose of STZ was injected intravenously either 2 weeks before or after initiation with DEN. The blood glucose levels were significantly elevated from 1 week after STZ-injection until autopsy. The numbers of GST-P positive foci at 1 week after DEN administration in the STZ-injected rats were similar to those in the non-diabetic rats. In contrast, both the numbers and areas of GST-P positive foci > 2 mm in diameter 8 weeks after DEN administration were increased significantly in the rats treated with STZ after DEN exposure compared with the non-diabetic control rats. The results suggest that hepatic preneoplastic lesions initiated with DEN are promoted by STZ treatment-inducing diabetes. <br>

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