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Gastroenterol Jpn. 1991 Feb;26(1):14-9.

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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1
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.

Abstract

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.

PMID:
1901045
DOI:
10.1007/bf02779503
[Indexed for MEDLINE]

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