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Biomedical subjects

B Schlatterer

Publications and source records attributed to B Schlatterer.

At least 37 records · Page 2Linked to original sources
PubMed1991

Discrimination of initiating and promoting carcinogens in fish.

Xiphophorine fish from wild populations are insusceptible of developing neoplasia. In contrast, certain backcrosses of Xiphophorus maculatus (platyfish) with Xiphophorus helleri (swordtail) as the recurrent parent produce offspring that develop neoplasia in a Mendelian fashion. We concentrated our research on melanoma. To construct a fish strain which is highly susceptible to mutagenic carcinogens, a particular regulatory gene, ie an oncosuppressor gene (Bs), was introduced into the fish developing the Mendelian inherited melanoma by introgression. Bs prevents the progeny from developing melanoma. However, Bs can be impaired by carcinogen-induced somatic mutation which gives rise to the development of clonal melanoma. Activity of the oncogene x-src (measured on pp60x-src kinase activity) and inositol lipid turnover is elevated in the tumor but, in contrast to the animals bearing the inherited melanoma, not in the brain. Tumor promoters do not induce melanoma in this strain. Similarly, in order to breed a fish strain which is highly susceptible to tumor promoters we introduced a regulatory gene, for instance an oncostatic gene (g) coding for a pretransformational arrest of pigment cell differentiation in the stem cell stage of the fish that develop the Mendelian inherited melanoma. The new strain is incapable of developing melanoma. Its x-src kinase activity and inositol lipid turnover is elevated in the brain, indicating that the biochemical processes which were found to be correlated with the hereditary melanoma formation, operate without the occurrence of melanoma. Following treatment of these animals with tumor promoters, melanoma develops within a very short latent period. Our tester strain can discriminate between tumor-initiating and tumor-promoting activities of agents of unknown carcinogenic potential.

Animals↗
PubMed1990

A host-mediated in vivo/in vitro assay with peritoneal murine macrophages for the detection of carcinogenic chemicals.

We have developed a host-mediated assay system for the detection of the transforming action of chemical carcinogens on peritoneal macrophages. Directly as well as indirectly acting carcinogenic substances administered intraperitoneally to NMRI mice could be examined in this way. Resident macrophages were recovered by peritoneal lavage from treated and untreated mice and were cultured in soft agar. After 5-6 days normal and transformed cells could be distinguished. Statistical analysis comparing cells, for example, from alpha-naphthylamine or diphenylhydantoin-treated animals with those from control mice proved that the test is positive at least on a significance level of 5% using the t-test. Further substances revealing a cell-transformation potential were benzene, benz(a)pyrene, 2,3,7,8-tetrachlorodibenzodioxin, N-nitrosodimethylamine, ethidium bromide, aflatoxin B1,N-methyl-N-nitrosourea, 1-methyl-3-nitro-1-nitrosoguanidine, 2-naphthylamine, dieldrin, suramin and trichloroethylene. A weak transforming potential was found for chlorambucil as well as for tetrachloroethylene. With toluene or azidothymidine no cell transformation could be observed. Several immortal cell lines could be established form NMRI mice treated with alpha-naphthylamine or N-methyl-N-nitrosourea. Athymic nu/nu mice injected subcutaneously with these cells developed tumors, establishing the oncogenic potential of these cell lines.

1-Naphthylamine↗
PubMed1990

Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver.

The effect of di(2-ethylhexyl)phthalate (DEHP) on diethylnitrosamine (DEN)-initiated preneoplastic liver lesions with expression of gamma-glutamyltranspeptidase (GGTase) and loss of adenosine triphosphatase (ATPase) as well as alterations of hepatic carbohydrate metabolism in male and female Sprague-Dawley rats have been investigated. Two treatment schedules have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic islands and by the biochemical determination of alterations in enzyme activities of liver homogenates and of serum, the last indicating hepatotoxicity. For initiation, a single dose of DEN was given, followed by treatment with various doses of DEHP given three times weekly by gavage for 7 or 11 consecutive weeks. As histochemical enzyme markers, the expression of positive GGTase as well as the deficiency in ATPase were used for identification of liver foci. The weanling female rats (protocol A) were found to be more sensitive to the carcinogenic effect of DEN in view of foci incidence than the mature male rats which underwent partial hepatectomy prior to DEN application. The administration of 200 mg DEHP/kg body wt increased the incidence of ATPase-deficient foci in both male and female rats; however, concentrations of 1000 and 2000 mg DEHP/kg decreased the incidence of liver foci. The number of foci with expression of GGTase was only slightly increased in female rats following a DEHP concentration of 50 mg/kg, and 200 mg/kg body wt. DEHP alone did not induce preneoplastic lesions that could be identified by these two markers. Biochemical investigations indicate that DEHP alters the metabolic pattern in liver. An increase of the NADP-linked enzymes glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, extra-mitochondrial ICDH as well as an enhancement of NAD-dependent alpha-G3PDH and lactate dehydrogenase were found following DEHP administration. On the other hand the glycolytic enzymes pyruvate kinase (PK) and enolase as well as the gluconeogenetic enzyme fructose-1,6-bisphosphatase (FBPase) were significantly reduced. In protocol B (male rats) the reactions of PK, FBPase and malic enzyme were more altered after DEHP exposure than in protocol A, while the activity of G6PDH was more increased in protocol A. Most enzymes being involved in the carbohydrate metabolism are influenced by DEHP in a dose-dependent manner. There was no increase in serum FBPase activity in both male and female rats after DEHP treatment but a reduction of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase activities was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Comparison of three rat liver foci bioassays--incidence of preneoplastic foci initiated by diethylnitrosamine.

Three rat liver foci bioassays have been compared with respect to their sensitivity by the histochemical demonstration of preneoplastic foci, and by the biochemical determination of alterations in enzyme activities of serum indicating hepatotoxicity. We studied the initiation/promotion schedules according to Oesterle and Deml (A), and according to Pereira (B, Broad Spectrum Protocol), and the initiation/selection protocol according to Tatematsu et al. (C), with diethylnitrosamine (DEN), given as a single initiating dose of 10 and 30 mg/kg body wt respectively. With all schedules Sprague-Dawley rats, either females, 3 weeks old (A), or males, 6 weeks old (B, C) were used. For promotion polychlorinated biphenyls (A) or phenobarbital (B) were administered. Selection was performed with 2-acetylaminofluorene (C). The rats in schemes (B) and (C) underwent partial hepatectomy one day prior to initiation. The number and total area of foci deficient in adenosine-5'-triphosphatase (ATPase) and positive in gamma-glutamyltranspeptidase (GGTase) was evaluated. In the complete schedule with 30 mg of DEN in system (A) foci incidence exceeded that of the other systems by about 7-fold (ATPase) and 2-fold (GGTase) respectively. The lower dose of DEN and all control experiments resulted in a respective lower foci yield. With scheme (C), but not with schemes (A) and (B), e.g. serum fructose-1.6-bisphosphatase and alkaline phosphatase were increased, suggesting liver cell damage. Thus tested with DEN, scheme (A) is most sensitive and causes a low impairment of animals' welfare.

2-Acetylaminofluorene↗
PubMed1987

Test guideline. Behavioral toxicity testing in animal experiments according to section 9, para. 1, No. 2 of the Chemicals Act (Chemikaliengesetz) of the Federal Republic of Germany.

The German Chemicals Act requires that chemicals are tested for behavioral toxicity at stage 2 of the testing procedure, i.e. if more than 1000 annual tons are produced. For this purpose a guideline was developed according to which data on behavioral toxicity are to be collected, which are based on cageside observations during longterm exposure. The protocol covers outer appearance, as well as motor, sensory, autonomic and central nervous system functions. Data are to be reported in tabular form and should be evaluated by taking all aspects of the toxicological profile into account.

Animals↗
PubMed1976

Transcriptional and post-transcriptional control of rRNA synthesis in human liver cells cultured in presence of L-triiodothyronine.

The synthesis of rRNA in cultured human liver cells grown in the presence of L-triiodothyronine (1.6 x 10(-5)M) was measured by means of polyacrylamide gel electrophoresis using a double labelling technique. The rate of accumulation of rRNA in the cytoplasm as well as the turnover of rRNA in ribosomes remained unchanged in comparison to control cells regardless of growth stage or cell population density. L-triiodothyronine, however, induced an increased synthesis of rpreRNA when added in the early growth phase of sparse cultures. This induction was time dependent and occurred temporarily, but it was never followed by a similar accumulation of mature rRNA. Therefore, in this system two control mechanisms counteracting each other were effective: the increased rpreRNA synthesis indicates a transcriptional control, and the wastage of odd rpreRNA, however, a post-transcriptional control.

Cells, Cultured↗