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The Bhas promotion assay is a cell culture transformation assay designed as a sensitive and economical method for detecting the tumour-promoting activities of chemicals. In order to validate the transferability and applicability of this assay, an inter-laboratory collaborative study was conducted with the participation of 14 laboratories. After confirmation that these laboratories could obtain positive results with two tumour promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and lithocholic acid (LCA), 12 coded chemicals were assayed. Each chemical was tested in four laboratories. For eight chemicals, all four laboratories obtained consistent results, and for two of the other four chemicals, only one of the four laboratories showed inconsistent results. Thus, the rate of consistency was high. During the study, several issues were raised, each of which were analysed step-by-step, leading to revision of the protocol of the original assay. Among these issues were the importance of careful maintenance of mother cultures and the adoption of test concentrations for toxic chemicals. In addition, it is suggested that three different types of chemicals show positive promoting activity in the assay. Those designated as T-type induced extreme growth enhancement, and included TPA, mezerein, PDD and insulin. LCA and okadaic acid belonged to the L-type category, in which transformed foci were induced at concentrations showing growth-inhibition. In contrast, M-type chemicals, progesterone, catechol and sodium saccharin, induced foci at concentrations with little or slight growth inhibition. The fact that different types of chemicals similarly induce transformed foci in the Bhas promotion assay may provide clues for elucidating mechanisms of tumour promotion.

We investigated changes in the extracellular levels of acetylcholine (ACh) following local application of serotonergic agents to the dorsal hippocampus of freely moving rats by means of perfusion using a microdialysis technique. Perfusion of serotonin (5‐HT; 10 μM, for 30 min at a rate of 3 μl/min), dissolved in Ringer's solution containing 10 μM eserine, showed no marked effect on the extracellular levels of ACh. 8‐Hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT; 20 μM), a 5‐HT1A agonist, increased ACh levels, whereas 7‐trifluoromethyl‐4‐(4‐methyl‐1 ‐piperazinyl)‐pymoto[1,2‐a]quinoxaline (CGS‐12066B; 100 μM), a 5‐HT1B agonist, decreased it. Clomipramine (2 μM), an uptake inhibitor of 5‐HT, had no effect on ACh levels. Following perfusion of 1‐(2‐methoxyphenyl)‐4‐[4‐ (2‐phthalimido)butyl]piperazine (NAN‐190; 10 μM), which is a selective 5‐HT1A antagonist, the effect of 8‐OH‐DPAT was totally abolished, whereas CGS‐12066B decreased extracellular ACh levels. 5‐HT, as well as Clomipramine, had a decreasing effect on ACh levels after pretreatment with NAN‐190. These results indicate that the 5‐HT1A receptor, which exists in the dorsal hippocampus, enhances the spontaneous ACh release, and that the mechanism of serotonergic modulation of ACh release partly depends on both the stimulatory control via the 5‐HT1A receptor and the suppressive one via the 5‐HT1B receptor in the dorsal hippocampus of rats.

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OBJECTIVE: To examine the effects of polaprezinc on morphologic change of the tongue epithelium and on cell cycle regulation of taste bud cells by using zinc-deficient rats, an animal model of taste disturbance. METHODS: After 28 days of feeding with zinc-sufficient or -deficient diet, the rats fed a zinc-deficient diet were divided into four groups in which 0, 1, 3 and 10 mg ⁄ kg of polaprezinc were administered for 28 days with continuation of diet. Histopathological and morphological examinations of the tongue were carried out. RESULTS: Parakeratosis was observed in all rats receiving the zinc-deficient diet and 1 mg ⁄ kg polaprezinc but not in rats receiving 3 and 10 mg ⁄ kg polaprezinc. The ratio of keratinizing epithelium in the outer and inner circumference were significantly increased from 9.6% and 11.3%, respectively, in zinc-sufficient rats to 36.9% and 32.9%, respectively, in zinc-deficient rats (P < 0.001 and <0.01). This increase was reversed to 13.7% and 12.3% in rats that received 3 and 10 mg ⁄ kg polaprezinc in the outer circumference, respectively. Same phenomenon was seen in the inner circumference part, 13.0% and 10.8% (P < 0.01), respectively. In addition, proliferating cell nuclear antigen-positive cells in the taste bud were significantly decreased from 75.5% in zinc-sufficient rats to 32.2% in zinc-deficient rats (P < 0.001). This decrease was reversed to 70.3%, 83.1% and 81.2% in rats that received 1, 3 and 10 mg ⁄ kg polaprezinc, respectively. CONCLUSION: Polaprezinc improves parakeratosis and decreases taste bud cell proliferation caused by zinc deficiency. These effects may be involved in mechanisms underlying improvement of taste disorders in animal models.