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Biomedical subjects

P Warnecke

Publications and source records attributed to P Warnecke.

At least 19 recordsLinked to original sources

Increased DNA methyltransferase expression in leukaemia.

Aberrant DNA methylation has been observed consistently in many human tumours, in particular in the CpG islands of tumour suppressor genes, but the underlying mechanism of these changes remains unclear. To determine whether DNA methyltransferase expression is increased in leukaemia, we developed a standardised competitive RT-PCR assay to measure the level of DNA methyltransferase transcripts. Using this assay on bone marrow RNA samples from 12 patients with acute leukaemia, we observed a 4.4-fold mean increase in the level of DNA methyltransferase mRNA compared with normal bone marrow. These results support but do not prove the hypothesis that an increase in DNA methyltransferase activity is associated with malignant haematological diseases and may constitute a key step in carcinogenesis.

Adult↗

[Investigation of alkylation in rat liver chromatin after application of 3H-cyclophosphamid--"fine-distribution" and kinetics].

The alkylation of chromatin constituents (DNA, histones and non-histones) in liver cell nuclei was investigated at various times after intraperitoneal injection of rats with 3H-cyclophosphamid. The highest alkylation was found in the DNA, the lowest in the histones; the euchromatic portions were alkylated several times higher compared to those of the heterochromatin. The eventual elimination of 3H-activity with time indicates that cyclophosphamid leads to repair processes in the DNA, this conclusion being supported by other experimental observations. In some of the 16 subfractions of the nonhistone proteins, alkylated portions are apparantly eliminated by normal protein turnover; however, in other nonhistones this elimination is inhibited, whereby in one subfraction it seems to be accelerated. The results of analog experiments with 14C-tryptophan as a precursor for nonhistone protein synthesis serve as a reference for this. In supplementary in-vitro model experiments using triaziquon as an alkylating agent indications for DNA-Protein-cross-links in chromatin could be obtained by the technique of X-ray low angle scattering, and according to sedimentation behaviour.

Alkylation↗

Studies on deoxyribonucleoproteins. IX. Subfractions of deoxyribonucleoproteins from rat and mouse liver.

By carrier-free continuous electrophoresis, deoxyribonucleoprotein from rat and mouse liver could be separated into two subfractions. The more anodic fraction (DNP I), comprising 5 - 8 per cent of the total, contains fewer proteins (two types of histones only). [3H]Cyclophosphamide caused in vivo a 2.5 times higher alkylation of the DNA in in DNP I than of the DNA in DNP II. These and additional results led to the suggestion of a structural model with DNP I as a spacer in the deoxyribonucleoprotein fiber.

Animals↗