The environmental contaminant benzo[a]pyrene (B[a]P) has been regarded as one of the pathogens of oral premalignant and malignant lesions. To elucidate the pathogenesis of oral premalignancies, B[a]P-induced dysplasia of the murine tongue was investigated for G1-associated cell cycle regulation. B[a]P solution was applied orally up to six weeks to induce epithelial dysplasia of the tongue. BrdU incorporation and the expression of p21, cyclin D1, and CDK4 were examined by immunohistochemistry and Western blotting. Rb phosphorylation and E2F-Rb binding were examined by immunoprecipitation and Western blotting. B[a]P treatment resulted in dysplastic changes and active DNA synthesis in the tongue epithelia. Immunohistochemical analyses showed p21 up-regulation and cyclin D1/CDK4 overexpression in B[a]P-induced dysplasia. Rb hyperphosphorylation and E2F release were caused by B[a]P treatment. Thus, dysregulation of G1-phase regulation is likely to be an important event in the development of oral epithelial dysplasia in mice.

  The purpose of this study was to clarify the effects of ingesting chloridquellen and bicarbonate spring waters on electrogastrography and heart rate variability in humans. The subjects were ten young adults (average age 21.9 years old). Three and six cycles per minute (cpm) frequency of electrogastrography (EGG) were measured, as well as the high-frequency (HF: 0.15-0.40Hz) components, and the ratio of low-frequency (LF: 0.04-0.15Hz) components to HF components in heart rate variability (HRV) during 90 minutes. The taste of the water and pain or abnormalities in the stomach were also assessed by having the subjects answer a questionnaire. The subjects ingested the spa water or purified water and were asked to respond to the questionnaire after thirty minutes, and they also ingested no water on a different day and were questioned. The EGG-6 cpm frequency, presumably reflecting intestinal activity, did not change under any conditions. The EGG-3 cpm frequency, presumably reflecting stomach activity, significantly increased with bicarbonate spring waters immediately after ingestion and decreased after 30 min. Additionally, the 3 cpm frequency significantly increased with ingestion of purified water over the course of 30 min. The HF components in HRV, presumably reflecting cardiac parasympathetic activity, did not change under any conditions. The ratio of LF to HF components in HRV, presumably reflecting cardiac sympathetic activity, significantly increased with ingestion of purified water immediately and after 15 min, and bicarbonate spring waters after 30 min. There was a difference between ingestion of chloridquellen and purified water in the answers concerning the taste of the water in the questionnaire. These findings suggest that the constituent parts of chloridquellen water and other factors activate stomach and autonomic nervous activities in humans.