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Induction of gastric mucosal cell proliferation by the fungicide captan: role of tyrosine kinases

Authors
Journal
Toxicology Letters
0378-4274
Publisher
Elsevier
Publication Date
Volume
54
Identifiers
DOI: 10.1016/0378-4274(90)90183-m
Keywords
  • Gastric Mucosal Dna Synthesis
  • Gastric Mucosal Thymidine Kinase
  • Gastric Mucosal Tyrosine Kinases
  • Captan
  • Protein Phosphorylation
  • Cell Proliferation
Disciplines
  • Biology
  • Chemistry
  • Medicine

Abstract

Abstract Captan (1,2,3,6-tetrahydro- N-trichloromethylthiophthalmide), a widely used fungicide, has been shown to induce carcinoma in the gastrointestinal tract of rodents. However, little is known about the captan induction of early biochemical changes in the gastrointestinal tract. The present investigation examines the changes in gastric mucosal proliferative activity in 2-month-old Fischer 344 rats following a daily injection (s.c.) of captan (100 mg kg body wt.) in DMSO while being infused (osmotic minipump) with the same compound (7.14 mg captan kg body wt. h ) for 2 weeks. The control rats received the vehicle the same way. The change in proliferative activity was related to tyrosine kinase (Tyr-k) activity and tyrosinespecific phosphorylation of protein(s) in gastric mucosal membranes since these intracellular events are thought to play an important role in proliferation, differentiation and transformation of cells. After 2 weeks of captan administration gastric mucosal DNA synthesis and thymidine kinase activity (indicators of proliferative activity) were increased by 330% ( P < 0.025) and 98% ( P < 0.025), respectively, when compared with the corresponding controls. Gastric mucosal DNA content was also increased by 90% ( P < 0.025) after administration of captan. These increases were associated with about 3-fold rise in Tyr-k activity and 2-fold increase in tyrosine phosphorylation of 6 mucosal membrane proteins with M r of 105, 90, 60, 55, 48 and 37 kDa. We conclude that captan stimulates gastric mucosal cell proliferation, and activation of Tyr-k and tyrosine phosphorylation of certain membrane proteins may be important in the regulation of this process.

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