Inhibition of hamster tongue carcinogenesis by selenium and retinoic acid.

The inhibitory effect of selenium, 13-cis-retinoic acid, and their combination was studied in an animal model in which squamous cell carcinoma of the tongue was induced by 0.5% 9,10 dimethyl-1,2 benzanthracene (DMBA). A controlled, blinded experiment was carried out using 60 Syrian hamsters divided into four groups of 15 each. When compared to controls, the mean day of carcinoma onset was delayed 3 weeks for animals given selenium, 6 weeks for animals given retinoic acid, and 5.5 weeks for animals given selenium plus retinoic acid. The differences between each experimental group and the control group are statistically significant. We conclude that both selenium and retinoic acid inhibit the development of DMBA-induced squamous cell carcinoma of the tongue in hamsters. The dose of retinoic acid used produces a stronger inhibitory effect, but is associated with significant toxicity. At the doses used, combined inhibitory effect is no greater than that for retinoic acid alone.

Selenium inhibition of chemical carcinogenesis in the upper aerodigestive tract of hamsters.

Evidence suggests that ingestion of selenium compounds may inhibit carcinogenesis. We studied this in hamsters in which squamous cell carcinoma of the tongue was induced with 0.5% dimethylbenzanthracene (DMBA). Forty-five hamsters, divided into three groups of 15 each, were fed a low-selenium diet and the left lateral border of the tongue was painted with DMBA three times a week. Control animals were given deionized water, while water for animals in groups 1 and 2 contained 3 and 6 ppm selenium, respectively. All sufficiently long-lived animals developed leukoplakia of the tongue and floor of the mouth that progressed to dysplasia and papillary or ulcerative carcinoma. Carcinomas were seen less frequently on the palate and in the pyriform sinuses. Carcinoma metastasized to neck lymph nodes in two hamsters. Data indicate a 2-week delay in leukoplakia incidence for the selenium groups; a higher survival rate was also noted, although this was not statistically significant. We conclude that this model is similar to tobacco-induced squamous cell carcinoma of the upper aerodigestive tract in humans and that ingestion of supplemental selenium produces a modest inhibitory effect on leukoplakia.

The effects of tryptophan and manipulations of serotonergic receptors on tonic immobility in chickens.

The effects of serotonergic manipulations on tonic immobility (TI) were examined. Systemic injections of tryptophan enhanced TI duration. This effect was reversed by quipazine, a 5-HT receptor agonist, and p-chloroamphetamine, a 5-HT releaser. Separately, these drugs caused marked reductions in TI duration. Fenfluramine, which promotes 5-HT release, also reduced TI duration. The quipazine attenuation of TI was prevented by pretreatment with the 5-HT receptor blocker cinanserin. The results are discussed in terms of 5-HT receptor mechanisms and the raphe model of tonic immobility.

Tonic immobility in domestic fowl: possible interaction of serotonergic and dopaminergic mechanisms.

Treatment with the dopamine (DA) receptor blocker, haloperidol, enhanced tonic immobility (TI) duration. Fenfluramine, a receptor agonist for serotonin (5-HT), reversed this effect. Tryptophan produced long TI reactions, and is believed to do so due to impaired synaptic transmission of 5-HT following its direct inhibitory effects on 5-HT neurons. DA receptor stimulation by apomorphine prevented the tryptophan potentiation of tonic immobility. The results suggest that serotonergic and dopaminergic systems may interact with respect to tonic immobility.