Induction of gastric GIST in rat and establishment of GIST cell line.

Continuous administration of the direct-reacting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine reportedly produces not only adenocarcinoma in rats, but also mesenchymal tumors. A large number of tumors diagnosed as gastrointestinal smooth muscle tumors actually represent gastrointestinal stromal tumors (GISTs) in human cases. We have induced mesenchymal tumors by duodenal reflux in rats. To clarify the differentiation of these mesenchymal tumors, immunohistochemical investigations were undertaken. In addition, the first culture model of GIST-DR derived from GIST induced by duodenal reflux was established. GIST-DR cells, both in vitro and in vivo, were strongly immunopositive for both KIT and CD34, and STI571 (Imatinib mesylate) blocked the proliferation of this cell line. The present results suggest that duodenal reflux plays a role in the histogenesis of GIST.