CAUSE AND EFFECT BETWEEN CONCENTRATION-DEPENDENT TISSUE-DAMAGE AND TEMPORARY CELL-PROLIFERATION IN RAT STOMACH MUCOSA BY NACL, A STOMACH TUMOR PROMOTER

This study was designed to test whether concentration or dose of NaCl was responsible for the initial tissue damage (after 1 min) and result ing temporary cell proliferation at 17 h in stomach mucosa of male F34 4 rats after gastric intubation of 0.65, 1.3, 2.6 and 3.7 M NaCl, Hist ological damage was studied by dual staining combining horseradish per oxidase-labeled Griffonia simplicifolia agglutinin-II staining (HRP-GS A-II) and periodic acid cold thionin-Schiff reaction (PATS), Cell prol iferation was studied by measuring replicative DNA synthesis with liqu id scintillation counting and by BrdU staining, NaCl at the same overa ll dose of 0.8 g/kg body weight induced different degrees of response depending on the concentration, For 4 ml of 0.65 M NaCl, there was no tissue damage after 1 min nor any increase in replicative DNA synthesi s after 17 h in the pyloric mucosa. Administration of 1.3 M NaCl (2 ml ), 2.6 M NaCl (1 ml) and 3.7 M NaCl (0.7 ml) induced concentration-dep endent damage of the surface mucous cell layer after 1 min and increas ed replicative DNA synthesis after 17 h (P < 0.05), Concentration-depe ndent increase in replicative DNA synthesis at 17 h was also induced w ith the same volume (1 ml) of 1.3, 2.6 and 3.7 M NaCl, while a volume- dependent increase in replicative DNA synthesis at 17 h was induced wi th 0.4, 0.7 and 1 ml of 3.7 M NaCl, However, a greater increase in rep licative DNA synthesis was always observed when using higher NaCl conc entrations at the same dose, Liquid scintillation counting was well-co rrelated with BrdU staining, These results suggest that a high concent ration of NaCl is responsible for the initial tissue damage and result ing temporary cell proliferation during stomach tumor promotion.