A morphologic and kinetic basis for the more invasive character of N-methyl-N'-nitro-N-nitrosoguanidine induced duodenal tumors following pyloroplasty.

Pyloroplasty increased the invasiveness of duodenal tumors in Wistar rats receiving N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 weeks (83 mg/l in drinking water) (Arch. Surg., 117, 768-771). To assess morphologic and kinetic alterations, analyses of tritiated thymidine (3HTdR) pulse-labeled fundic, antral and duodenal mucosa were carried out. The normal appearance of MNNG-treated antral and duodenal mucosa was characterized by the appearance of elongated hyperactive columns exhibiting elevated levels of DNA synthesis. Pyloroplasty in carcinogen-treated rats induced both a 3-fold enhancement in the number of these elongated columns and an elevation in the number of proliferating cells within them (P less than 0.001). In the MNNG and pyloroplasty treated duodenal mucosa 26% of columns contained over 130 cells/column rather than an average of 100 cells in normal appearing MNNG-treated mucosa. DNA synthesis was increased by 23% within these hyperactive glands (11.3 proliferative cells/column vs. 9.4/column in normal appearing mucosa). Pyloroplasty creates both an increase of gastric bile reflux and an increase of the gastric evacuation rate, conditions which influence cell proliferation. Such alterations in antro-pyloro-duodenal physiology contribute to the increased cellular activity observed, promote malignant transformation and foster the expression of invasiveness.