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F Anders

Publications and source records attributed to F Anders.

At least 37 records · Page 2Linked to original sources
PubMed1988

v-erbB related sequences in Xiphophorus that map to melanoma determining Mendelian loci and overexpress in a melanoma cell line.

Certain genotypes of Xiphophorus harbour an accessory Mendelian gene which following loss, impairment, or insufficiency of its regulatory genes in the germ line, mediates the hereditary capacity to develop neoplasia spontaneously or following induction with initiating and promoting carcinogens. Together with its linked regulatory genes it forms a 'tumor gene-complex' (Tu-complex). We concentrated on accessory sex chromosomal Tu-complexes that are responsible for sex chromosome-linked melanoma formation. Southern analyses of the xiphophorine genome with 15 authentic oncogene probes revealed so far that only three v-erbB related EcoRI fragments comprising 4.9 kb of a certain X-, 11.5 kb of another X-, and 6.7 kb of both a Y- and Z-chromosome are inherited in parallel with the Tu-complex and melanoma formation. They are accessory in the genome, and are highly homologous with each other. The sequence of the X-chromosomal 4.9 kb fragment shows minor but significant differences to that of the invariably present autosomal xiphophorine erbB (x-erbB) fragment of 5.5 kb, indicating that at least two different x-erbB genes coding for different EGF receptors can exist in the fish. Northern analyses showed expression of both genes in a fibroblast cell line, and overexpression of the sex chromosomal x-erbB in a melanoma cell line. The co-segregation of the hereditary trait of melanoma with the sex chromosomal x-erbB fragments, suggests that the accessory x-erbB gene may be responsible for the switch from the normal to the neoplastic state of the pigment cells.

Amino Acid Sequence↗
PubMed1984

Xiphophorus as an in vivo model for studies on oncogenes.

The capacity of Xiphophorus to develop neoplasia can be formally assigned to a "tumor gene" (Tu), which appears to be a normal part of the genome of all individuals. The wild fish have evolved population-specific and cell type-specific systems of regulatory genes (R) for Tu that protect the fish from neoplasia. Hybridization of members of different wild populations in the laboratory followed by treatment of the hybrids with carcinogens led to disintegration of the R systems permitting excessive expression of Tu and thus resulting in neoplasia. Certain hybrids developed neoplasia even spontaneously. Observations on the genuine phenotypic effect of the derepressed Tu in the early embryo indicated an essential normal function of this oncogene in cell differentiation, proliferation and cell-cell communication. Tu appeared to be indispensable in the genome but may also be present in accessory copies. Recently, c-src, the cellular homolog of the Rous sarcoma virus oncogene v-src, was detected in Xiphophorus. The protein product of c-src, pp60c-src, was identified and then examined by its associated kinase activity. This pp60c-src was found in all individuals tested, but, depending on the genotype, its kinase activity was different. The genetic characters of c-src, such as linkage relations, dosage relations, expression, etc., correspond to those of Tu. From a systematic study which showed that pp60c-src was present in all metazoa tested ranging from mammals down to sponges, we concluded that c-src has evolved with the multicellular organization of animals. Neoplasia of animals and humans is a characteristic closely related to this evolution. Our data showed that small aquarium fish, besides being used successfully because they are time-, space-, and money-saving systems for carcinogenicity testing, are also highly suitable for basic studies on neoplasia at the populational, morphological, developmental, cell biological, and molecular levels.

Animals↗
PubMed1982

The induction of a specific pigment cell type by total genomic DNA injected into the neural crest region of fish embryos of the genus Xiphophorus.

We report genetic transformation in an intact higher organism, i.e., in xiphophorine fish. The gene to be transferred (Tu) is responsible for the formation of T-melanophores in the platyfish and is involved in the formation of melanomas in platyfish-swordtail hybrids. After injection of Tu-donor DNA into the neural crest region of embryos from Tu-free fish, some of the recipients developed T-melanophores. In a few cases, one or two single T-melanophores were formed during late embryo-genesis. In most cases, many T-melanophores developed in young fish and were arranged in several colonies or in a pattern. DNase-degraded Tu-donor DNA, Tu-free fish DNA, as well as DNA from E. coli and adenovirus-2, did not induce T-melanophores. When using DNA from different strains of Tu-donor fish which differed in a regulating gene linked to Tu, the percentages of fish showing T-melanophores paralleled the degree of phenotypic expression of the Tu gene in the DNA donor. The results suggest that the Tu gene has been successfully transferred together with the linked regulating gene.

Animals↗
PubMed1982

Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus.

Neoplastic transformation of pigment cells in the teleostean fish Xiphophorus is mediated by a cellular oncogene (Tu). Normally. Tu is suppressed by multiple regulating genes (R). Depending on impairment and loss of R genes, Tu is permitted to express itself phenotypically. In the pigment cell system, different degrees of Tu expression lead to small spots of transformed cells or to benign or malignant melanoma. All neoplastic and nonneoplastic cells of all Xiphophorus genotypes tested thus far appear to contain the cellular homolog (c-src) of the avian sarcoma virus oncogene (v-src). The evidence for this stems from the detectability of a Mr 60,000 phosphoprotein with associated kinase activity (pp60c-src) that reacts with antiserum against viral pp60src. We followed the inheritance of Tu (identified by spots and melanomas) compared to the expression of c-src identified by the pp60c-src-associated protein kinase). By quantitative determination of kinase activity in immunoprecipitated pp60c-src from fish showing different degrees of Tu expression, we have investigated whether there exists a correlation between the expression of c-src and Tu. In genotypes with the same genetic background, cells from Tu-containing fish express more pp60c-src than do cells from fish lacking Tu. In genotypes carrying a Tu gene and which show differences in the amount of gene expression due to a different extent of repression by regulating genes, analysis of kinase activity revealed that an increase of Tu expression is correlated with an elevated level of pp60c-src-associated kinase activity. Our findings may indicate that c-src activity in Xiphophorus is modulated by the Tu gene product or that Tu and c-src are regulated coordinately.

Animals↗
PubMed1981

[Hereditary and environmental factors in the causation of neoplasia based on studies in Xiphophorus (author's transl)].

The genetic information for neoplastic transformation is inherited as a normal part of the genome in all individuals of Xiphophorus. Neoplasia, however, was found only in hybrids between members of different populations and local races. It can be classified in (a) a large group that is triggered by mutagens, (b) a large group that is triggered by mutagens, (b) a large group triggered by promoters, (c) a small group that develops, "spontaneously", and (d) a small group that is inherited according to Mendelian Laws. The process leading to susceptibility for neoplasia is represented by the disintegration of coadapted gene systems that normally protect the fish from neoplasia. Hybridization is the most effective process that leads to disintegration of the protection gene-systems. Environmental mutagens and promoters (i.e. carcinogens) may complete disintegration and thus may trigger neoplasia. The phenomenon of introducing susceptibility to neoplasia by means of hybridization has been observed in a large variety of plants and animals (Table 2). While we have no data on the relation between hybridization and cancer in human beings comparable to those in plants and animals, we put the question whether the many facts on tumor incidence in humans, that do not agree with the concept of the primacy of environmental factors in carcinogenesis may be explained by interpopulational and interracial hybridization in preceding generations. Based on our studies on Xiphophorus we suppose that environmental factors represent only the peak of an iceberg in the multistep process of the causation of neoplasia. The most important steps leading to neoplasia, i.e. those that bring out susceptibility, are supposed to be hidden in our ancestry.

Animals↗
PubMed1981

Cytogenetics of neoplasia of Xiphophorus.

Certain laboratory hybrid Xiphophorus fish develop heritable neoplasia. Neoplasia can also be induced in some hybrids by treatment with carcinogens. In either case the neoplasms are mediated by a "'tumor gene," that is normally controlled by linked or nonlinked "regulating genes" or both. Light and electron microscopic studies on these two types of tumors reveal important differences. The heritable tumor is a compact mass of tissue formed of densely packed melanized melanocytes often with nuclear pockets and projections. A large number of cells undergoing a process of nuclear fragmentation has been observed. The induced tumors, on the other hand, contain fewer melanized melanocytes and show a comparative increase in the amount of connective tissue. The nuclear pockets and projections commonly found in the melanocytes of the heritable tumors are not present in the melanocytes of the induced melanoma. The most important difference observed was the presence of different types of structural chromosome aberrations in the induced tumor and a total absence in the heritable ones. These anomalies seem to be epiphenomenal, and the real genetic change is subchromosomal.

Animals↗
PubMed1979

Cell cultures derived from embryos and melanoma of poeciliid fish.

In poeciliid fish, melanoma of different degrees of malignancy can be produced by crossing specific genotypes. For a detailed investigation of the processes leading to proliferation or differentiation of the melanoma cells, it is necessary to establish cell cultures. The aim of the present study was to find out the optimal conditions for initiating and culturing poeciliid fish cells for the purpose of establishing cell cultures of melanoma. The optimal method was developed by using small pieces of late embryos as starting material and includes: (a) dispersion of tissue by mild stepwise treatment with a trypsin-EDTA mixture at low temperature; (b) culture of cells in the complex medium 199; (c) supplementation of medium with high percentage (20%) of fetal bovine serum; and (d) stabilization of pH by buffering the medium with HEPES. Under these conditions, primary and secondary cultures of embryonic cells have been initiated. An epithelial-like cell line has been subcultured for more than 80 passages. The method developed for embryonic tissues was used to start cell cultures from melanoma of platyfish-swordtail hybrids. Until now, only cells of rapidly growing malignant albino melanoma could be maintained in primary cultures. Secondary cultures could not be initiated since the melanoma cells tended to differentiate and stopped growing before a confluent monolayer was formed.

Animals↗