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Biomedical subjects

R Wiger

Publications and source records attributed to R Wiger.

33 records · Page 2Linked to original sources
PubMed1985

In vitro testing for developmental toxicity using the Hydra attenuata assay.

The developmental hazard of six chemicals was tested in vitro in the Hydra attenuata assay which is based upon the differential toxicity between the adults and a regenerating stage known as an artificial "embryo". The toxicity of DMSO, ethyl alcohol, lindane and paracetamol was similar for both adults and embryos. On the other hand, sodium valproate and isoniazid was, respectively, seven and 100 times more toxic for embryos than adults, thus indicating that these pharmaceuticals might pose developmental hazards to mammalian development. The differential toxicities seen in the Hydra assay reflect analogous data on laboratory animals.

Acetaminophen↗
PubMed1984

Evidence for flavivirus(es) outside of the distribution area for Ixodes ricinus in Norway.

Small rodent (vole) sera were collected from three different locations in Norway. One of these was within the distribution area for Ixodes ricinus, and a tick-borne encephalitis (TBE) virus strain had been isolated from ticks collected there (Traavik & Mehl, 1977). The two other locations were outside the I. ricinus area, one in southern Norway, the other at nearly 70 degrees N. The sera were tested for TBE antibodies by hemagglutination inhibition (HI), hemolysis-in-gel (HIG) and complement fixation (CFT). All sera were also tested for HI antibodies to Uukuniemi (UUK) virus, and some positive TBE HI reactions were verified by separation of immunoglobulins and serum lipoproteins in NaBr gradients. Animals containing TBE virus antibodies reacting in all three serological tests and animals with UUK HI antibodies were detected only from the location within the I. ricinus area. From the two locations outside the I. ricinus area we found animals which had antibodies reacting with TBE virus in HI and HIG, but not in CFT. Antibodies to UUK were not detected. The results indicate that flavivirus(es) related to, but not identical with TBE viruses are transmitted by other vectors than I. ricinus in parts of Norway.

Animals↗
PubMed1979

Lemming cycles in captivity.

2 freely growing confined populations of Norwegian lemmings displayed population peaks and declines which were similar to natural populations. In most other studies of confined populations of rodents, the number of animals stabilized and maintained fairly constant numbers. Juvenile mortality and reduced pregnancy rate contributed to the decline.

Animals↗
PubMed1979

Scanning electron microscopic studies on males of trichinella species.

Ultrastructure of the cuticle and pseudobursa of adult males of four species of Trichinella has been studied by SEM. T. nativa differs markedly from T. spiralis, T. nelsoni and Trichinella sp. in the form of the pseudobursa. Trichinella sp. differs only slightly from T. spiralis and T. nelsoni. The ultrastructure of the cuticle revealed no characters suitable for the differentiation of the taxons under study.

Animals↗
PubMed1978

The first tick-borne encephalitis virus isolates from Norway.

Five virus strains with close serological relationship to the tick-borne encephalitis (TBE) complex have been isolated from Ixodes ricinus ticks. The ticks were collected in early June 1976 at three different locations in Sogn & Fjordane County, Norway. One of the virus-yielding pools was composed of ticks collected between the cabins on a tourist camping ground.

Animals↗
PubMed1978

California encephalitis group viruses isolated from mosquitoes collected in Southern and Arctic Norway.

Three virus strains serologically related to the California encephalitis group (Bunyaviridae) of arboviruses were isolated from 7331 mosquitoes collected in Norway in June-August 1975. Two of the isolates (S 548 and S 618) seemed to be closely related and the third, S 568, more distantly related by serological techniques to Tahyna virus. Viruses were found in the mosquito species Aedes sticticus, A. diantaeus and A. hexodontus colllected (in order) from Oyern (59 degrees N, 11 degrees 12' E), Trandum (60 degrees 08' N, 11 degrees 10' E) and Masi (69 degrees 26' N, 23 degrees 39' E). The Masi isolate seems to be the northernmost arbovirus isolate in the world so far. Strain S 568 was from 16 male A. diantaeus, indicating transovarial transmission of the virus. An accidental infection demonstrated the potential human pathogenicity of one of the newly-isolated strains (S 568), and the ability of CE viruses to persistently infect suckling mouse brains was indicated by in vivo findings. The biological characteristics of the new strains so far investigated are consistent with those of the California encephalitis group. During this work the Aerosil absorption method for production of haemagglutinating antigens proved useful for Tahyna virus and the newly-isolated strains. Trypsinization of erythrocytes improved the haemagglutinating capacities of these viruses.

Animals↗
PubMed1978

Fatal experimental Babesia microti infections in the Norwegian lemming, Lemmus lemmus (L.).

Experimental infections of Babesia microti in laboratory-reared Clethrionomys glareolus revealed that approximately 15% of the erythrocytes were infected with single ring forms during peak parasitemia. Infected erythrocytes could be detected in blood smears up to one month post infection. C. glareolus treated with a single injection of Depo-Medrol i.m. two days prior to infection displayed a four-fold increase in number of infected erythrocytes at peak parasitemia, 35% of which contained more than one Babesia, and a prolongation of the infection. B. microti infections in 35 laboratory--reared Lemmus lemmus were fatal. Multiple invasion of erythrocytes, anemia, icterus, hemoglobinuria, anorexia and weight loss, and adrenal and splenic hypertrophy were characteristic for B. microti infections in Norwegian lemmings.

Animals↗
PubMed1978

Hematological, splenic and adrenal changes associated with natural and experimental infections of Trypanosoma lemmi in the Norwegian lemming, Lemmus lemmus (L.).

Both natural and experimental Trypanosoma lemmi infections in Norwegian lemmings caused slight anemias and hypoglycemia. Leucocyte counts remained the same. Adrenal and splenic hypertrophy were associated with natural infections whereas only splenic hypertrophy was present in the experimental infection. Grahamella sp. infections were also associated with adrenal and splenic hypertrophy in wild lemmings. It is suggested that blood parasites which are associated with anemia, hypoglycemia and adrenal hypertrophy might also interfere with both male and female reproduction, and should be considered in the interpretation of the population regulation of small rodents.

Adrenal Glands↗
PubMedDate not supplied

Effects of acetaminophen and hydroxyurea on spermatogenesis and sperm chromatin structure in laboratory mice.

High doses of acetaminophen (400 mg/kg) or hydroxyurea (200 mg/kg) given intraperitoneally daily for 5 d caused reduction in relative testicular weight in mice (B6C3/F1/BOM M). Testicular atrophy of several tubules was seen in the hydroxyurea-treated mice 5 d after the last exposure, whereas acetaminophen did not lead to such changes. Exposure to acetaminophen caused neither a depletion of glutathione in the testis nor a marked increase in covalent binding. In contrast, significant decreases in the incorporation of thymidine into the testis were observed during the first 3 h following a single treatment with acetaminophen (100 to 400 mg/kg) or hydroxyurea (100 to 200 mg/kg). In mice treated with acetaminophen (400 mg/kg) or hydroxyurea (200 mg/kg) daily for 5 d, flow cytometric analysis revealed large reductions in one of the tetraploid populations of testicular cells (mostly early pachytene spermatocytes) on days 5 and 10. Changes in the populations of the various spermatid stages occurred later; thus, both compounds appeared to cause a delay in spermiogenesis. Indications of abnormal chromatin structure were seen in an increased frequency of vas deferens sperm on days 27 and 33 after the last exposure, when measured as increased susceptibility towards DNA denaturation in situ. In conclusion, high doses of acetaminophen or hydroxyurea inhibit DNA synthesis in the testis. The present data indicate that this leads to reduced testicular weight, a reduction in the number of early pachytene spermatocytes, changes in the proportions of the various spermatid stages, and an apparent alteration in sperm chromatin structure.

Acetaminophen↗
PubMedDate not supplied

In vitro toxicity of 1,2-dibromo-3-chloropropane (DBCP) in different testicular cell types from rats.

1,2-Dibromo-3-chloropropane (DBCP)-induced toxicity was studied in rat germ cells from different stages of spermatogenesis, separated by centrifugal elutriation, and in Sertoli cells prepared from sexually mature and immature animals. The in vitro metabolic activation of 50 to 250 microM DBCP, measured as covalent binding of 14C-DBCP to macromolecules, was highest in round spermatids, lowest in Sertoli cells and elongating/elongated spermatids, and intermediate in spermatocytes. High concentrations of DBCP (> or = 250 microM) caused a decrease in oxygen consumption and mitochondrial rhodamine 123 uptake, indicating an effect on mitochondrial function. Altered Sertoli cell function, measured as detachment of germ cells in Sertoli-germ cell cocultures, was evident at DBCP concentrations > or = 300 microM. DBCP-induced DNA damage occurred at much lower concentrations (10 to 30 microM) when compared to effects on mitochondrial function and Sertoli cell function. The extent of single strand DNA breaks and alkali-labile sites (ssDNA breaks) measured by the alkaline filter elution technique and the single cell gel electrophoresis assay, were greatest in the round spermatids > spermatocytes = Sertoli cells > elongating/elongated spermatids. The study demonstrates that various testicular cell types show differences in their rates of activation of DBCP to metabolites that bind to macromolecules. DNA is a more sensitive intracellular target in DBCP-induced testicular toxicity than mitochondria. Round spermatids appear to be more susceptible to DBCP-induced ssDNA breaks than spermatocytes, elongating/elongated spermatids, or Sertoli cells.

Animals↗
PubMedDate not supplied

DNA strand breaks in testicular cells from humans and rats following in vitro exposure to 1,2-dibromo-3-chloropropane (DBCP).

Preparations of testicular cells from human organ transplant donors and from Wistar rats were compared with respect to their composition of the different testicular cell types, their ability to metabolize 1,2-dibromo-3-chloropropane (DBCP), and their relative sensitivity to induction of DNA single strand breaks and alkali labile sites (ssDNA breaks) after treatment with DBCP, 4-nitroquinoline N-oxide (4-NQO), and X rays. Flow cytometric and microscopic analysis demonstrated that the interindividual variation in the composition of testicular cell types was considerably greater in the human tissue than in that from rats. The in vitro metabolic activation of DBCP (50 to 250 microM), measured as radiolabel covalently bound to macromolecules, was three-fold faster in rat testicular cells compared to human testicular cells. X rays (1 to 10 Gy) and 4-NQO (0.5 to 2.5 microM) induced ssDNA breaks to a similar extent in both human and rat testicular cells as measured by single cell get electrophoresis (SCGE) and alkaline filter elution. In contrast, 1,2-dibromo-3-chloropropane (DBCP) (3 to 300 microM) caused no significant DNA damage in human testicular cells, whereas in rats there was a clear concentration-dependent increase in ssDNA breaks. The data show that, compared to rats, testicular cells from humans are less efficient in activating DBCP to metabolites binding covalently to macromolecules. However, from the rate of covalent binding observed one would expect a significant degree of DBCP-induced ssDNA breaks in the human testicular cells. The low level of DBCP-induced ssDNA breaks in human testicular cells could indicate that different reactive DBCP metabolites are involved in binding to cellular macromolecules compared to DNA damage, or that different rates of DNA repair exist in human and rat testicular cells.

4-Nitroquinoline-1-oxide↗
PubMedDate not supplied

A comparative study of chemically induced DNA damage in isolated human and rat testicular cells.

Testicular cells prepared from human organ transplant donors or from Wistar rats were used to compare 15 known reproductive toxicants with respect to their ability to induce DNA damage, measured as single-strand DNA breaks and alkali labile sites (ssDNA breaks) with alkaline filter elution. The compounds tested included various categories of chemicals (i.e., pesticides, industrial chemicals, cytostatics, and mycotoxins) most of which are directly acting genotoxicants (i.e., reacting with DNA either spontaneously or via metabolic activation). In addition, a few indirect genotoxic and nongenotoxic reproductive toxicants were included. Six of the chemicals induced no significant levels of ssDNA breaks in human and rat testicular cells; methoxychlor (10 to 100 microM, human and rat), benomyl (10 to 100 microM, human and rat), thiotepa (10 to 1000 microM, human and rat), cisplatin (30 to 1000 microM, human; 100 to 1000 microM, rat), Cd2+ (30 to 1000 microM, human; 100 to 1000 microM, rat), and acrylonitrile (30 to 1000 microM, human; 30 to 300 microM, rat). Four chemicals induced significant levels of ssDNA breaks in testicular cells from both species: styrene oxide (> or = 100 microM, rat and human), 1,2-dibromoethane (EDB) (> or = 100 microM, rat; 1000 microM human), thiram (> or = 30 microM, rat; > or = 100 microM, human), and chlordecone (300 microM, rat; > or = 300 microM, human). Finally, five chemicals induced ssDNA breaks in one of the two species. Four chemicals induced significant ssDNA breaks in rat testicular cells only: 1,2-dibromo-3-chloropropane (DBCP) (> or = 10 microM), 1,3-dinitrobenzene (1,3-DNB) (> or = 300 microM), Cr6+ (1000 microM), and aflatoxin B1 (> or = 100 microM), the last two of these produced only a minor positive response. One chemical, acrylamide, induced a marginal increase in ssDNA breaks in human at 1000 microM, but not in rat testicular cells. Although based on a limited number of donors, the data indicate a close correlation between the induction of DNA damage in human and rat testicular cells in vitro. For some chemicals, however, there appears to be differences in the susceptibility to chemically induced ssDNA breaks of isolated testicular cells from the two species. The data indicate that the parallel use of human and rat testicular cells provides a valuable tool in the assessment of human testicular toxicity.

Adult↗
PubMedDate not supplied

Expression of CYP2B1 in freshly isolated and proliferating cultures of epithelial rat lung cells.

Bronchiolar Clara cells and alveolar type 2 cells of the lung are known to express relatively high levels of P450 enzymes compared to other pulmonary cells. Populations of enriched type 2 cells and Clara cells were isolated from rat lung by a procedure including lung perfusion, protease digestion, centrifugal elutriation, and differential attachment. Alveolar macrophages were removed by lavage. The purity of the type 2 cell-enriched population was approximately 90%, and the purity of the Clara cell-enriched population was 40-50%. Both type 2 cells and the cells of the Clara cell-enriched population proliferated in culture. CYP2B1 mRNA was expressed approximately to the same level in type 2 cells and the Clara cell-enriched population. The mRNA levels remained roughly constant for both cell types throughout the culture period, except for an early transient reduction. The apoenzyme level of CYP2B1 was 2-3 times higher in freshly isolated cells of the Clara cell-enriched population than in the type 2 cells. Both epithelial cell types showed decreased level of CYP2B1 apoenzyme in culture. The differences in the CYP2B1 mRNA and apoenzyme expression levels in freshly isolated cells and cultured cells suggest the existence of a post-transcriptional regulatory mechanism for CYP2B1 expression in lung cells. The characterization of specific functions of lung cells in culture, such as P450 gene expression, provides necessary information for the use of the cells in in vitro pulmonary toxicology.

Animals↗