Exposure to ionizing radiation increases responsiveness to neural secretory stimuli in the ferret jejunum in vitro.

Experiments were designed to determine the effects of ionizing radiation on jejunal epithelial function in the ferret in vitro. Basal and stimulated electrolyte transport were determined in Ussing chambers at 0.5, 2, 24 and 48 h post-irradiation. Tissue histamine and 5-hydroxytryptamine levels were measured. Myeloperoxidase activity was also measured as an index of inflammation. Basal short circuit current was reduced at 2 h post-irradiation, but was elevated at 48 h. Basal conductance was significantly increased by 24 and 48 h. Responsiveness to electrical field stimulation was depressed at 0.5 h, and was greater than control by 24 and 48 h post-irradiation. Similarly, short circuit current responses to prostaglandin E2 were depressed at 0.5 h and elevated at 24 h. No significant change was observed in the response to carbachol post-irradiation, indicating that alterations in responsiveness were not likely at the level of the enterocyte. Changes in responsiveness to electrical field stimulation correlated significantly with increases in mucosal mast cell numbers. Myeloperoxidase activity, indicative of neutrophil infiltration, did not increase post-irradiation, nor was there histological evidence of an inflammatory cell infiltrate. There were no changes in tissue histamine or 5-hydroxytryptamine. Histology also revealed little microscopic morphological change from shams in tissue from irradiated ferrets. The results of this study demonstrate effects of irradiation on electrolyte transport in the ferret jejunum. The enhanced neurally evoked electrolyte transport observed at 24-48 h post-irradiation was not correlated with the development of inflammation, but was correlated with changes in mast cell numbers.

Ionizing radiation reduces neurally evoked electrolyte transport in rat ileum through a mast cell-dependent mechanism.

BACKGROUND/AIMS: Mechanisms of neuroimmune regulation of intestinal electrolyte transport under pathophysiological conditions are unclear. This study investigated the effect of ionizing radiation on ileal electrolyte transport. METHODS: Rats were exposed to 10 Gy gamma-radiation and were killed 2, 24, and 48 hours later. Ileal segments were either mounted in Ussing chambers and exposed to electrical field stimulation, prostaglandin E2, leukotriene D4, or theophylline, or they were assayed for biochemical indices of inflammation. Other segments were processed for routine histological screening, mast cell counts, or immunohistochemical analysis of the distribution of vasoactive intestinal polypeptide or substance P immunoreactivity. RESULTS: Basal short-circuit current was unchanged 2, 24, or 48 hours postirradiation. However, there was a reduction of tissue responsiveness to electrical field stimulation, prostaglandin E2, and theophylline but not to leukotriene D4. Decreased responsiveness at 2-hours postirradiation was blocked by pretreatment with the H1 antagonist pyrilamine. Tissue myeloperoxidase activity and 5-hydroxytryptamine content were not altered postirradiation, but tissue histamine and mucosal mast cells were significantly reduced at 24 and 48 hours. There were no significant changes in villus-crypt architecture until 48 hours postirradiation. There was no significant alteration in the distribution of immunoreactive vasoactive intestinal polypeptide or substance P. CONCLUSIONS: Ionizing radiation reduced the transport response to neural stimulation. The effect correlated temporally with decreased mast cells and histamine, suggesting a functional role for previously reported mast cell-nerve interactions.

Dexamethasone: a potent blocker for radiation-induced taste aversion in rats.

Rats, trained to drink water during a single 30-min period each day, were then given 0.1% saccharin twice a week and water on other days for 30 min. If 20 rad of radiation (0.2 Gy) were given each time 30 to 40 min after the saccharin the rats developed a profound aversion to saccharin during the course of three weeks, whereas control groups failed to do so. This paradigm was then used to test the ability of drugs, given twice weekly immediately after the saccharin, to prevent the development during three weeks of an aversion when 20 rad was given, 30 to 40 min later. Insulin, domperidone, haloperidol, acetylsalicylic acid, naloxone, chlorpheniramine, cimetidine, and dimethyl sulphoxide were tested without notable success. However dexamethasone, at doses ranging from 0.013 mg/kg to 1.3 mg/kg, significantly attenuated the conditioned taste aversion by up to 60 percent. The results are discussed in terms of a search for an antinauseant and antiemetic drug effective against radiation in man.

Quantitative studies of cytological damage in mouse testis produced by exposure to heat.

Damage in gonadal cells produced by exposure of the hindquarters of conscious male mice to water at temperatures up to 43 degrees C was studied by measuring the percentage of testicular cells which do not exclude trypan blue 4 h after exposure, sperm count up to ten wk later, and the percentage of morphologically abnormal sperm up to ten wk later. It was found that the percentage of cells stained with trypan blue was significantly increased by exposure for 0.5 h at 41 degrees C or 2 h at 37 degrees C. Sperm count and the percentage of abnormal sperm were affected by 0.5 h at 43 degrees C or 2 h at 40 degrees, but not by lower temperatures. Since there is a high incidence of abnormal sperm after some heat treatments, the use of this assay for mutagen screening should be approached with caution.

Modification of survival of gamma irradiated mice by adenosine nucleotides.

The administratio prior to irradiation of adenosine triphosphate (ATP) or other adenosine nucleotides, singly or in combination, increased the radioresistance of mice. Post-irradiation treatment with the adenosine nucleotides had no effect on the survival of the irradiated mice. Dose reduction factors of 2.32 could be obtained by pretreatment of mice with the following combination of protective agents: S-2(4-aminobutylamino)ethyl phosphorothioic acid(WR 2822), cysteamine (MEA) and ATP. Since cyclic AMP levels were unchangd in the spleen or gut by administration of cysteamine and other protectors it is unlikely that the increase in preotection was due to changes in cyclic AMP levles. The calcium salt of ATP provided a higher level of protection than the ATP alone, indicating that the protective mechanism of ATP is probably not related to anoxia.