The inhibitory effect of anti-tumor drugs on phosphatidylcholine synthesis and its reversal by geranylgeranylacetone in the isolated guinea pig gastric glands.
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.
Nishisaki
H
H
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Sakamoto
C
C
Konda
Y
Y
Nakano
O
O
Matozaki
T
T
Matsuda
K
K
Wada
K
K
Nagao
M
M
Kasuga
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002433:Cefaclor / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005641:Tegafur / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D000970:Antineoplastic Agents; D004224:Diterpenes; D008937:Mitomycins; D010713:Phosphatidylcholines; D005641:Tegafur; D016685:Mitomycin; D002433:Cefaclor; D003520:Cyclophosphamide; C031049:geranylgeranylacetone; D005905:Glyburide