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Triethylenemelamine induced dominant lethals in mice--comparisons of oral versus intraperitoneal injection.

We have compared the relative effectiveness of oral and i.p. injections of triethylenemelamine (TEM) in inducing dominant lethality in male mice. The standard dominant lethal protocol was used in these experiments. TEM, when injected i.p. resulted in significant increased in fetal mortality during the first three weeks post-treatment. Decreases in the number of implants per pregnant female were noted during this same period, with only minor decreases in fertility. In contrast, oral injections of TEM resulted in only fluctuations in the percent of fetal mortality. In addition, oral injections of TEM did not result in significant differences in either total implants or percent fertility. Possible causes of the observed differences between these two routes of administration are discussed.

Administration, Oral

Localization of mercury in CNS of the rat. II. Intraperitoneal injection of methylmercuric chloride (CH3HgCl) and mercuric chloride (HgCl2).

The autometallographic method has been used to determine the precise localization of mercury in the brain and spinal cord of adult Wistar rats which had been treated with repeated ip injections of methylmercuric chloride (CH3HgCl; 0.2 to 10.0 mg) or mercuric chloride (HgCl2; 0.2 to 10.0 mg). The distribution of mercury was uneven following administration of HgCl2, while it was fairly homogeneous following CH3HgCl. With both compounds, however, heavy deposits of mercury were present in the motor nuclei of rhombencephalon. In contrast, cerebellar Purkinje cells, Golgi cells, and Golgi epithelial cells only contained mercury in sections from rats exposed to CH3HgCl. In cerebral sections from rats exposed to CH3HgCl, staining intensity in cortical cells varied among the layers, being greatest in laminae III, V, and VI. On the other hand, sections from rats exposed to HgCl2 showed only staining in scattered cells of lamina VI. Following administration of either compound, mercury was detected in the gray matter of the spinal cord mercury. Particularly large deposits were present in the anterior horn motoneurons. At the cellular level, the heaviest staining intensity was seen in neurons, although the cytoplasm of glia and ependymal cells also showed significant deposits in sections from rats exposed to CH3HgCl. In HgCl2-treated rats, the largest accumulations of mercury were seen in the neurons. The ependymal cells were stained to a lesser extent, while glia were devoid of mercury. Ultrastructurally, mercury deposits were located exclusively in lysosomes. The present results demonstrate that the pattern of mercury distribution and its staining intensity in individual cells in the rat CNS are dependent upon the chemical structure of the compound and the duration of its administration.

Animals

Tissue distribution and clearance of tritium-labeled dihydromicrocystin-LR epimers administered to Atlantic salmon via intraperitoneal injection.

The two epimers of [3H]dihydromicrocystin-LR (spec. act. 32.6 microCi/mumole) were synthesized by reduction of microcystin-LR, a cyclic heptapeptide hepatotoxin, with sodium boro[3H]hydride. In Atlantic salmon, following an i.p. injection of the epimers (0.1 mg of toxin/100 g), the toxins were; after 2 hr, concentrated in the liver and pyloric caeca and intestine; after 5 and 22 hr, concentrated in the liver; and after 46 hr concentrated in the liver and kidney. The maximum concentration in the liver, 4.9 +/- 0.5% of the injected dose, was observed at 5 hr. At 46 hr the incorporation of tritium in the liver was 2.4%. The total whole body incorporation of tritium label at 2, 5, 22 and 46 hr was 67.9 +/- 7.3%, 78.4 +/- 3.1%, 54.5 +/- 6.6% and 12.2%, respectively. The per cent levels of incorporation are significantly lower and the clearance rates are significantly higher than those observed in mice. The ratio of relative concentrations of radiolabel observed in the livers and flesh indicates that extremely low levels of microcystin-LR would be present in the flesh of fish afflicted with 'netpen liver disease'. Coupled with further evidence, it is suggested that the consumption of Atlantic salmon suffering from 'netpen liver disease' does not represent a potential human health hazard.

Animals

Differentiation of cytotoxic adherent cells from peroxidase positive cells after intraperitoneal injection of Brucella abortus organisms.

The relations between the cytotoxic adherent cells (CAC) and the peroxidase positive adherent cells (PPAC) which appeared after i.p. injection of Brucella abortus were investigated. A kinetic study showed that PPAC preceeded CAC. Twenty-four hours after bacterial injection, almost all adherent cells stained for peroxidase and no cytotoxic activity could be recorded. Cells sampled at this moment acquired cytotoxic properties by cultivation in LPS containing medium. The treatment of the bacterial organisms by HCl or chloroform: methanol (C:M) suppressed their ability of inducing CAC but not that of inducing LPS-activatable PPAC. The substances extracted by C:M could activate PPAC into CAC in vitro. The data presented suggest that CAC differentiate from PPAC, that the recruitment of PPAC is not always followed by their transformation into CAC and that different components of the bacterial organisms might be necessary to achieve the steps of cell recruitment and maturation.

Animals

Lead distribution in the saliva and blood fractions of rats after intraperitoneal injections.

Sprague-Dawley rats were treated with 1, 2 or 3 i.p. injections of lead acetate (100 mg/kg) and sacrificed 24 h, 3 days, 7 days, 14 days and 21 days after the last injection. Lead concentration was determined by flameless AAS technique in whole blood, plasma, plasma filtrate, saliva and submaxillary gland tissue. The concentration of lead in saliva was about 5% of whole blood lead concentration and around 61% of plasma filtrate lead level. Saliva lead concentration was significantly related both to whole blood lead concentration and plasma filtrate lead concentration (r = 0.78, P less than 0.001; r = 0.80, P = 0.001 respectively). Lead was present in the submaxillary gland tissue; the amount of lead increased with increasing amounts administered.

Animals

Comparison of acute toxic effects of intraperitoneally injected nitromethane and nitroethane in rats.

Male 3-month-old Wistar rats dosed i.p. with 200 mg/kg of nitromethane or -ethane showed increased acid proteinase activity in the brain 4 h after the injection. The change was accompanied by a marginal increase in the cerebral glutathione concentration. Nitroethane caused enhanced epoxide hydrolase and UDP-glucuronosyltransferase activity in the hepatic microsomal fraction up to 48 h while 7-ethoxycoumarin o-deethylase decreased. These biochemical changes were accompanied by proliferation of smooth endoplasmic reticulum and degranulation and disorganization of the rough endoplasmic reticulum of the nitroethane-exposed liver cells. The hepatic effects of nitromethane were restricted to decreased cytochrome c reductase activity with proliferation of smooth endoplasmic reticulum. The results point at limited peroxidative damage possibly involving reduction of the nitrogroup.

7-Alkoxycoumarin O-Dealkylase

The influence of l-methionine-d,l-sulfoximine on the labelling of acid soluble fraction and proteins of the brain cortex after intraperitoneal injection of 14c-leucine.

Methionine sulfoximine (MSO) inhibits the labelling of the acid soluble fraction and proteins of the brain cortex after the injection of 14C-leucine. The inhibition takes place even during the early stages after the injection of MSO, when no symptoms of paroxysms are observable. The action of MSO on the labelling of the acid soluble fraction and proteins in the brain cortex is obviously different from that in the kidney and liver. Whereas in the brain tissue MSO markedly influences the labelling of the free amino acid pool, in the kidney and liver it seems primarily affect the protein synthetic mechanisms. Also no decrease in labelling of the plasma acid soluble fraction was found on mice, treated with MSO. Experimental data support the idea, that the changes in the metabolism of proteins in the brain are not connected with the onset of the paroxysmal period.

Animals