The tumorigenic potential of aluminum potassium sulfate [A1K (SO4)2 12H2O, APS], a compound which exists widely in the environment, was investigated in B6C3F1 mice. APS was administered in the diet for 20 months at dose levels of 1.0, 2.5, 5.0 and 10.0% (w/w). One group receiving the basal diet served as the control. Body weight gain in both sexes was decreased in the 10.0% APS treated group, and increased in the 1.0 and 2.5% APS treated groups. The survival rates at the end of the dosing period were 73.3% (male) and 78.3% (female) in the control group, and 86.7-95.0% (male) and 86.7-91.7% (female) in the APS treated groups. The survival rate showed a tendency to increase in both sexes in all the APS treated groups. In the tumor pathology, the incidence of hepatocellular carcinoma was significantly decreased in the males in the 10% APS treated group. The incidence of hepatocellular carcinoma was significantly decreased in females in all groups including the control group. As regards the nontumorous pathology, the incidence of myocardial eosinophilic cytoplasm showed a significant dose-dependent decrease in males in the APS treated groups. A comparison between the sexes revealed a significant decrease in the incidence of hepatocytic anisonucleosis, myocardial eosinophilic cytoplasm and acinar cell vacuolation of the submandibular gland in the females; and lymphocyte infiltration in renal cortex and pelvis, and vacuolation of cerebellar white matter were noted in the males. The results of the present study indicate that long-term administration of APS does not exert tumorigenic or any other toxic actions in B6C3F1 mice.

Alum Compounds↗

PubMedDate not supplied

Induction of malignant fibrous histiocytoma in female Fisher rats by implantation of cyanoacrylate, zirconia, polyvinyl chloride or silicone.

Five kinds of foreign bodies (silicone, cellulose, polyvinyl chloride, zirconia and alkyl-alpha cyanoacrylate) were implanted into subcutaneous tissue of female Fisher rats. Subcutaneous tumors were induced in 27.3, 54.5, 100, 63.6% of rats by silicone rubber, polyvinyl chloride, zirconia and alkyl-alpha-cyanoacrylate, respectively, but not by cellulose. Almost all tumors were composed of a mixture of cells that resembled fibroblasts characterized by the presence of numerous rough-surfaced endoplasmic reticulum and Golgi apparatus, histiocytes characterized by developed endoplasmic reticulum and abundant lysosome, myofibroblasts characterized by the presence of both myofibrils and fibroblast-like structures, and immature mesenchymal cells. In some tumors, the cells exhibited a storiform pattern. Some tumor cells were positively stained by ED2 or anti-muscle actin antibody. The features of induced tumors in rats were consistent with those of human malignant fibrous histiocytoma. A rat malignant fibrous histiocytoma transplanted into the subcutaneous tissue of the syngeneic female Fisher rats grew and metastasized to the lungs.

Animals↗

PubMedDate not supplied

Pharmacological characteristics of DQ-2511 as a prokinetic agent.

The pharmacological characteristics of DQ-2511, a substituted benzamide (3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide), as a prokinetic agent were studied. Cholecystokinin-octapeptide, dopamine, and alpha-calcitonin gene-related peptide, all suppressed gastric emptying in mice. Reversal of the depressed emptying occurred when DQ-2511 was administered by the oral or intraperitoneal route. When the action of eight proposed metabolites of DQ-2511 on the mouse cholecystokinin-octapeptide model was investigated, the main metabolite in plasma, MA-2, showed no effect, although two minor metabolites ameliorated or aggravated the delayed gastric emptying. This finding implies that DQ-2511, as the parent compound itself, exerts the ameliorative action. In dogs treated with cisplatin or copper sulfate, DQ-2511 had no antiemetic activity, as assessed by the number of vomiting episodes. The concern that the mechanism of action of DQ-2511 was blockade of receptors for cholecystokinin-octapeptide, dopamine, serotonin, alpha-calcitonin gene-related peptide, nicotine or muscarine, was resolved by results of radioligand binding studies showing the absence of a DQ-2511 binding to any of these receptor types. Evidence is accumulating that the mechanism of the prokinetic action of DQ-2511 involves the intrinsic and extrinsic autonomic innervation.

Administration, Oral↗