Flow cytometric analysis of the effect of sodium chloride on gastric cancer risk in the rat.
Dietary sodium chloride has been identified, both experimentally and epidemiologically, as a risk factor for gastric cancer. In order to elucidate the manner in which salt increases gastric tumor incidence in N-methyl-N'-nitro-N-nitrosoguanidine-treated animals, flow cytometric cell cycle analyses were performed on rats which had been treated with 1 ml of a solution of saturated NaCl by gavage and sacrificed 0, 1, 6, 12, 24, or 48 h after treatment. The gastric antra were excised, disaggregated, and stained with propidium iodide for cell cycle analysis. Results showed that there is a reduction in cell yield at early time points due to the toxicity of NaCl, followed by a net increase in the number of cells in the S phase of the cell cycle at 24 h. Treatment of rats with NaCl 24 h prior to a dose of 10 micrograms of 3H-labeled N-methyl-N'-nitro-N-nitrosoguanidine did not lead to an increase in alkylation of DNA isolated from mucosal cells. Therefore, the hypothesis that salt enhances gastric cancer risk from N-methyl-N'-nitro-N-nitrosoguanidine by disruption of the "mucosal barrier" leading to an increased effective dose to target cells is not supported by the results of these experiments. Several studies have shown that cells in S phase are the most susceptible to mutagenesis and that increasing the number of cycling cells in a target organ will increase tumor incidence (e.g., partial hepatectomy). Thus it is possible that NaCl increases gastric cancer risk through the mitogenesis which results from the damage caused to the mucosa by this agent.
D000818:Animals; D001345:Autoradiography; D002453:Cell Cycle; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000187:drug effects; D008297:Male; D008745:Methylation; D008769:Methylnitronitrosoguanidine; D051381:Rats; D011919:Rats, Inbred Strains; D012306:Risk; D012965:Sodium Chloride / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; D004247:DNA