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Inhibition of gastric tumorigenesis byα-difluoromethylornithine in rats treated with N-methyl-N′-nitro-N-nitrosoguanidine

  • Original Papers
  • Experimental Oncology
  • Published:
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Abstract

Male Wistar rats were treated concurrently with a combination of the carcinogenN-methyl-N′-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7) and the polyamine-synthesis inhibitor α-difluoromethylornithine (DFMO) at two different doses of 0.5% and 1.0% (w/v). Experimental groups were treated with (I) MNNG alone (n=25), (II) MNNG plus 0.5% (w/v) DFMO (n=25), (III) MNNG plus 1.0% (w/v) DFMO (n=25), (IV) 1.0% (w/v) DFMO alone (n=25). Group V represented untreated controls (n=20). Both the carcinogen and DFMO were administered in drinking water. The treatment time with the carcinogen and DFMO was 35 weeks. After treatment was completed animals were followed for an additional 50 weeks to cover a total observation time of 85 weeks. Significantly fewer animals developed gastric adenocarcinoma in the two groups of animals that received a combined treatment of MNNG plus DFMO compared to animals treated with the carcinogen alone (P<0.05 and 0.005). No benign or malignant neoplastic lesions were observed in the stomach or duodenum of animals treated with DFMO alone or in untreated controls.

It is concluded that concurrent treatment with DFMO prevents the development of malignant gastric epithelial tumors induced by MNNG in rats.

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Abbreviations

MNNG:

N-methyl-N′-nitro-N-nitrosoguanidine

DFMO:

α-difluoromethylornithine

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Authors and Affiliations

  1. Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, W-6900, Heidelberg, Germany

    Thomas Lehnert & Klaus Buhl

  2. German Cancer Research Center, Heidelberg, Germany

    Stanislaw Ivankovic

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  1. Thomas Lehnert
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  2. Klaus Buhl
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  3. Stanislaw Ivankovic
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Supported in part by a grant from Deutsche Forschungsgemeinschaft Le 466/3-1

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Lehnert, T., Buhl, K. & Ivankovic, S. Inhibition of gastric tumorigenesis byα-difluoromethylornithine in rats treated with N-methyl-N′-nitro-N-nitrosoguanidine. J Cancer Res Clin Oncol 119, 594–598 (1993). https://doi.org/10.1007/BF01372722

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  • DOI: https://doi.org/10.1007/BF01372722

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