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The inhibitory effect of anti-tumor drugs on phosphatidylcholine synthesis and its reversal by geranylgeranylacetone in the isolated guinea pig gastric glands

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Summary

To clarify the mechanism by which the administration of anti-tumor drugs, antibiotics or hypoglycemic agents causes gastric mucosal injury, the effects of these drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands were examined in vitro. Anti-tumor drugs such as tegafur, cyclophosphamide, and mitomycin C decreased [3H]choline incorporation into phosphatidylcholine. Furthermore, tegafur at 0.4 mg/ml decreased [3H]choline incorporation in the glands that had been pulsed with [3H] choline incorporation, suggesting that tegafur exerts its effect by inhibiting late step of phosphatidylcholine synthesis in the stomach. On the other hand, cefaclor and glibenclamide had no effect on [3H]choline incorporation. Geranylgeranylacetone, an anti-ulcer drug partially restored tegafur-induced reduction of [3H] choline incorporation into phosphatidylcholine. These results suggest that the anti-tumor drug-induced gastric mucosal injury may be due to drug-induced decrease in phosphatidylcholine synthesis, which the restoration of phosphatidylcholine synthesis by geranylgeranylacetone may explain its anti-ulcer action on drug-induced gastric mucosal lesions in vivo.

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Authors and Affiliations

  1. Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, 650, Kobe, Japan

    Hogara Nishisaki, Choitsu Sakamoto M.D., Yoshitaka Konda, Osamu Nakano, Takashi Matozaki, Kohei Matsuda, Ken Wada, Munehiko Nagao & Masato Kasuga

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  1. Hogara Nishisaki
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  2. Choitsu Sakamoto M.D.
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  3. Yoshitaka Konda
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  4. Osamu Nakano
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  5. Takashi Matozaki
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  6. Kohei Matsuda
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  7. Ken Wada
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  8. Munehiko Nagao
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  9. Masato Kasuga
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Nishisaki, H., Sakamoto, C., Konda, Y. et al. The inhibitory effect of anti-tumor drugs on phosphatidylcholine synthesis and its reversal by geranylgeranylacetone in the isolated guinea pig gastric glands. Gastroenterol Jpn 26, 14–19 (1991). https://doi.org/10.1007/BF02779503

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  • DOI: https://doi.org/10.1007/BF02779503

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