Interaction between N-methyl-N'-nitro-N-nitrosoguanidine and 2 steroid hormones in the glandular stomach of mouse. I. Acceleration of hydrocortisone turnover by use of a salt-rich diet and the carcinogen.
The present study has investigated the question of whether or not hydrocortisone as a gene regulator plays a role in the expression of carcinogenic and cocarcinogenic actions of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and NaCl at the gastric epithelium. The interaction of local hydrocortisone, MNNG and NaCl was studied in vitro and in vivo using Swiss/ICR mice of both sexes. MNNG inhibited specific hydrocortisone binding with the cytoplasmic receptor from the glandular stomach of mouse. The intake of both excess NaCl and MNNG induced an increase in hydrocortisone turnover in the glandular stomach of mouse. Likewise, administration of either excess NaCl or MNNG increased the activity of ornithine decarboxylase in the glandular stomach of mouse. Long-term use of a salt-rich diet and MNNG drink induced an irreversible reduction in water consumption without affecting NaCl consumption, a dissociation of the hydrocortisone effect. The aforementioned MNNG effect on water turnover was more marked in female than in male mice. It is suggested that NaCl and MNNG produce a state of corticosteroid stimulation and androgen depression at the glandular stomach epithelium of mouse--a reproduction of the hormonal markers of gastric cancer.
Kodama Research Institute of Preventive Medicine, Nagoya, Japan.
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D000818:Animals; D004347:Drug Interactions; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology*; D013270:Stomach / Q000201:enzymology
D011965:Receptors, Glucocorticoid; D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; D009955:Ornithine Decarboxylase; D006854:Hydrocortisone