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Metabolism of the hamster pancreatic carcinogen methyl-2-oxopropylnitrosamine by hamster liver and pancreas

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Summary

Background. The mechanism whereby methyl-2-oxopropylnitrosamine (MOP) is activated remains unknown. To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices and homogenates from Syrian hamsters and rats.

Methods. After the incubations, disappearance of 100 µM MOP and appearance of a metabolite was followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection.

Results. Disappearance rates were 1.2 nmol/mg protein/h for hamster liver slices; zero for hamster pancreatic slices, ducts and acini; zero for rat liver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for hamster liver homogenate and cytosol, and hamster pancreas homogenate and microsomes, respectively. The principal MOP metabolite was identified as methyl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its 1H-NMR and mass spectra. MHP yields were generally similar to MOP consumption, but were zero for hamster pancreatic homogenate despite its ability to metabolize MOP.

Conclusion. MOP is a pancreatic carcinogen in hamsters but not in rats. In metabolic studies, hamster liver slices and homogenate (especially the cytosol) produced MHP from MOP. This is probably an inactivation reaction. Hamster pancreas homogenate (especially the microsome fraction), but not rat pancreas homogenate, metabolized MOP without forming MHP, indicating another route of metabolism, perhaps activation to give the proximal carcinogen.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 68198-6805, Omaha, NE

    Terence A. Lawson & Sidney S. Mirvish

  2. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 68198-6805, Omaha, NE

    Sidney S. Mirvish

  3. Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 68198-6805, Omaha, NE

    Sheng C. Chen, Xiaojie Wang, Lin Zhou, Carol Kolar, Terence A. Lawson & Sidney S. Mirvish

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  1. Sheng C. Chen
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  2. Xiaojie Wang
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  3. Lin Zhou
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  4. Carol Kolar
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  5. Terence A. Lawson
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  6. Sidney S. Mirvish
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Correspondence to Sidney S. Mirvish.

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Chen, S.C., Wang, X., Zhou, L. et al. Metabolism of the hamster pancreatic carcinogen methyl-2-oxopropylnitrosamine by hamster liver and pancreas. International Journal of Pancreatology 27, 105–112 (2000). https://doi.org/10.1385/IJGC:27:2:105

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  • DOI: https://doi.org/10.1385/IJGC:27:2:105

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