Stimulation of cell division in the rat by NaCl, KCl, MgCl2, and CaCl2, and inhibition of the sodium chloride effect on the glandular stomach by ascorbic acid and beta-carotene

Three questions associated with the stimulation of cell division by chlorid e salts have been investigated: (i) whether cations other than sodium show a similar effect, (ii) whether vitamins can have a preventive activity, and (iii) whether subchronic treatment with sodium chloride in the diet is als o effective. Male Fischer 344 rats were given solutions of the chloride sal ts of sodium, potassium, magnesium, and calcium by oral gavage. Water was u sed for control. After 4 h, a 24-h osmotic minipump containing 5-bromo-2'-d eoxyuridine was implanted subcutaneously. The forestomach and glandular sto mach, as well as liver and bladder were analyzed immunohistochemically 24h later for the proportion of cells in S phase as an indicator of the rate of replicative DNA synthesis. For both the forestomach and the glandular stom ach, potassium was as potent as sodium, and the divalent cations Mg and Ca were even more potent on a molar basis. Supplementation of the diet with as corbic acid (2 g/kg food) or beta-carotene (12.5 mg/kg food) for 1 week bef ore gavage of the sodium chloride solution resulted in an inhibition of the stimulation of cell division. A putative tumor-chemopreventive activity of the two vitamins might therefore not only rely on their antioxidative prop erties but may include effects on the cell cycle. A 4-week treatment with a sodium chloride supplement in the diet (2% and 4% supplement) resulted in a significant stimulation of cell division not only in both parts of the st omach and in the bladder (with the 4% supplement) but also in the liver (ev en with the 2% supplement). Sodium-chloride-stimulated cell turnover theref ore is a sustained effect.