The protein encoded by the Drosophila position-effect variegation suppressor gene Su(var)3-9 combines domains of antagonistic regulators of homeotic gene complexes.

Modifier mutations of position-effect variegation (PEV) represent a useful tool for a genetic and molecular dissection of genes connected with chromatin regulation in Drosophila. The Su(var)3-9 gene belongs to the group of haplo suppressor loci which manifest a triplo enhancer effect. Mutations show a strong suppressor effect even in the presence of PEV enhancer mutations, indicating a central role of this gene in the regulation of PEV. By molecular analysis, Su(var)3-9 could be correlated with a 2.4 kb transcript which encodes a putative protein of 635 amino acids containing a chromo domain and a region of homology to Enhancer of zeste and trithorax, two antagonistic regulators of the Antennapedia and Bithorax gene complexes, as well as to the human protein ALL-1/Hrx which is implicated in acute leukemias. This region of homology is found in all four proteins at the C-terminus. The homology of Su(var)3-9 to both negative (Polycomb and Enhancer of zeste) and positive (trithorax) regulators of the Antennapedia and Bithorax complexes also suggests similarities in the molecular processes connected with stable transmission of a determined state and the clonal propagation of heterochromatinization.

P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster.

P transposon induced modifier mutations of position-effect variegation (PEV) were isolated with the help of hybrid dysgenic crosses (pi 2 strain) and after transposition of the mutator elements pUChsneory+ and P[lArB]. Enhancer mutations were found with a ten times higher frequency than suppressors. The 19 pUChsneory(+)- and 15 P[lArB]-induced enhancer mutations can be used for cloning of genomic sequences at the insertion sites of the mutator elements via plasmid rescue. Together with a large sample of X-ray-induced (48) and spontaneous (93) enhancer mutations a basic genetic analysis of this group of modifier genes was performed. On the basis of complementation and mapping data we estimate the number of enhancer genes at about 30 in the third chromosome and between 50 and 60 for the whole autosome complement. Therefore, enhancer of PEV loci are found in the Drosophila genome as frequently as suppressor genes. Many of the enhancer mutations display paternal effects consistent with the hypothesis that some of these mutations can induce genomic imprinting. First studies on the developmentally regulated gene expression of PEV enhancer genes were performed by beta-galactosidase staining in P[lArB] induced mutations.

Non-selective action of 4-hydroxyanisole on melanoma cells in vivo.

In order to clarify the role of tyrosinase (E.C. 1.14.18.1) in the cytotoxicity of 4-hydroxyanisole (4HA) in vivo, we have compared the therapeutic effects of 4HA on the B16 melanoma and Harding-Passey melanoma, which differ significantly in their tyrosinase content. The observed therapeutic effects are moderate and similar in both tumors. Therefore, there is no evidence for an increase of the cytotoxic effect of 4HA by tyrosinase in vivo. Application of 4HA to mice carrying B16 melanoma and Harding-Passey melanoma results in an inhibition of [3H]-TdR incorporation into melanoma DNA as well as into DNA of liver, intestine, kidney, and spleen. There is no selective activity on melanoma cells by 4HA in vivo. Therefore, in the therapy of human melanoma by 4HA, side effects on normal tissues cannot be excluded.

[Synthesis of 5-bromosalicyl-4'-chloroanilide-O-beta-D-xylopyranoside and other transport forms enzymatically activated by microbes]. / Synthese des 5-Bromsalicyl-4'-chloranilid-O-beta-D-xylopyranosids und weiterer durch Mikroben enzymatisch aktivierbarer Wirkstoff-Transportformen.

The synthesis of 5-bromosalicyl-4'-chloroanilide-O-beta-D-xylopyranoside and other glycosides of 5-bromosalicyl-4'-chloroanilide, salicylanilide, 3,5-dichlorophenol and tetrachlorohydrochinone is described. Glycosidations follow the procedures described by Latham et al. Sabalitschka and Helferich et al. These glycosides represent relatively untoxic transport-forms of drugs, which are activated to the free drug by specific enzymes of the organisms to be destroyed. This new mechanisms can help to destroy fungi and parasites in dermatology, agriculture, horticulture and cultivation of decorative plants without side effects on the host.

[Synthesis and properties of digitoxigenin-3 beta-O-alpha-L-arabinofuranoside]. / Synthese und Eigenschaften des Digitoxigenin-3 beta-O-alpha-L-arabinofuranosids.

The synthesis of a cardenolide glycoside with a furanoide sugar component, digitoxigenin-3 beta-O-alpha-L-arabinofuranoside (4), is described for the first time. 4 was prepared by the reaction of digitoxigenin with 2,3,5-tri-O-benzoyl-alpha-L-arabinofuranosylchloride and Fétizon-reagent in benzene/dioxan followed by debenzoylation with ammonia in dry methanol. Compound 4 is cleaved by alpha-L-arabinofuranosidase (Aspergillus niger K1) into digitoxigenin and L-arabinose. Hydrolytic stability against methanolic HCl (0.1 mol/l) is relatively high. 4 X 10(-8) mol/l 4 gives a 50% inhibition of the Na,K-ATPase (pig heart muscle) and is 2.5 times more active at this receptor than the aglycon digitoxigenin.

[Situation and perspectives of tumor chemotherapy from experimental viewpoint (author's transl)]. / Zur Situation und Perspektive der Tumorchemotherapie aus experimenteller Sicht.

In a reveiw article the origin, the present position, and the possibilities of further development of tumour chemotherapy are described. The central problems in preparing new substances and combinations with more selective activity, and different forms of carriers with promising perspectives are discussed.

Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme.

Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs.