Induction of Ornithine Decarboxylase and Tumor Promotion by N-Methyl-N′-Nitro-N-Nitrosoguanidine, Sodium Chloride, and Dimethyl Itaconate

  • Aeree moon, Aeree-Moon (Department of Biochemical Pharmacology, National Institute of Safety Research (NISR)) ;
  • Kim, Dae-Joong (Department of Histopathology National Institute of Safety Research (NISR)) ;
  • Han, Beom-Seok (Department of Histopathology National Institute of Safety Research (NISR)) ;
  • Hwang, Moon-Ok (Department of Histopathology National Institute of Safety Research (NISR)) ;
  • Kim, Chang-Ok (Department of Histopathology National Institute of Safety Research (NISR)) ;
  • Choi, Kwang-Sik (Department of Histopathology National Institute of Safety Research (NISR))
  • Published : 1993.12.01

Abstract

The possible tumor-promoting activities of sodium chloride (NaCl) and dimethyl itaconate (DMI), one of the quinone reductase inducers, were examined on stomach of male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administrations of NaCl and DMI after the initiation by MNNG resulted in various sized masses in the rat forestomach. Histopathologic studies showed that the combination of NaCl and DMI made an enhancing effect on the MNNG-induced carcinogenesis, resulting in papilloma in 5 weeks and squamous cell carcinoma in 20 weeks in submucosal area of forestomach. We also used an in vivo shortterm method for evaluating possible tumor-promoting activity with ornithine decarboxylase (ODC) as a marker. The markable inductions of the ODC activities by MNNG, NaCl, and DMI were found in the pyloric mucosa of rat stomach in time-dependent manners. A single administration of MNNG induced ODC activity up to 288 pmol $CO_2$/hr/mg protein at 24 hr after the administration. NaCl caused induction of ODC with a maximum of 179 pmol $CO_2$/hr/mg protein at 8 hr after the administration. ODC was induced up to 539 pmol $CO_2$/hr/mg protein at 16 hr after the administration of DMI. Additional treatment of NaCl and NaCl plus DMl caused 2 fold and 7 fold increases, respectively, in the ODC activity of the MNNG-alone group at 24 hr after the administration. These results suggest that NaCl and DMI have promoting activities in the rat gastric carcinogenesis initiated by MNNG.

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