PubMed Health⌕ Search

Biomedical subjects

F Arwert

Publications and source records attributed to F Arwert.

89 records · Page 5Linked to original sources
PubMed1982

Cytogenetic toxicity of antitumor platinum compounds in Fanconi's anemia.

Peripheral blood lymphocytes of patients with Fanconi's anemia (FA) were tested for their susceptibility to chromosome breakage by cis-platinum(II)-diamminedichloride [cis-Pt(II)], cis-platinum(IV)diamminetetrachloride [cis-Pt(IV)], and trans-platinum(IV)diamminetetrachloride [trans-Pt(IV)]. Low doses (0.1 microgram/ml) of the DNA-DNA cross-linking agents cis-Pt(II) and cis-Pt(IV) dramatically increased the chromosome breakage level in FA cultures without affecting the controls. The predominantly DNA-protein cross-linking compound trans-Pt(IV), however, was much less effective in producing chromosomal damage in FA. The differential response of FA cells to cis-Pt(IV) and trans-Pt(IV) suggests that the high susceptibility of FA to bifunctional cross-linking agents is due to an impairment of the cells to tolerate DNA-DNA cross-links, rather than DNA-protein cross-links.

Anemia, Aplastic↗
PubMed1981

Oxygen-dependence of chromosomal aberrations in Fanconi's anaemia.

Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by a high frequency of 'spontaneous' chromosomal aberrations and an increased risk of cancer. If, as seems plausible, the microscopically visible chromosomal aberrations in this disorder result from DNA or chromatin damage that would normally be repairable, the questions arise as to which step (or steps) in the repair process is deficient and whether the deficiency is intrinsic or the result of secondary factors. We report here that the frequency of chromosomal aberrations in FA lymphocyte cultures is positively related to oxygen tension and suggest that the site primarily affected by the FA mutation is in the complex system of defence (that is, protection and repair) against the genetic toxicity of oxygen.

Adult↗
PubMed1979

Erythrocyte superoxide dismutase deficiency in Fanconi's anaemia established by two independent methods of assay.

Erythrocyte superoxide dismutase (SOD; E.C.1.15.1.1) levels were quantitated in human haemolysates, both by an immunological technique and by an activity assay. The erythrocyte SOD activity level in a group of seven Fanconi's anaemia patients was significantly decreased (27%, on the average) compared to a control group of nineteen healthy individuals. The fact that both the activity per antigenic unit and the electrophoretic mobility of the erythrocyte SOD was normal indicates that the deficiency in these Fanconi's anaemia patients is most probably not due to a mutation in the structural gene for the enzyme but more likely due to a disturbed mechanism regulating the SOD level in the erythrocyte.

Anemia, Aplastic↗
PubMed1976

Induction of prophage SPO2 in Bacillus subtilis: isolation of excised prophage DNA as a covently closed circle.

Bacillus subtilis tryC2, thyA, thyB, lysogenic for the phage DNA polymerase negative mutant SPO2 susL244, was induced under conditions preventing phage and bacterial DNA synthesis. The biological activity of DNA from induced cells and from uninduced controls was assayed by transformation and transfection, respectively. About 50% of the phage DNA biological activity in DNA extracted from induced cells was resistant to exposure to pH 11.8 TO 11.9. This DNA was operationally defined as alkali-resistant phage DNA. Transforming bacterial DNA from uninduced or induced cells and transfecting DNA from uninduced cells were more than 95% inactivated after exposure to high pH. The alkali-resistant phage DNA was characterized by sucrose gradient centrifugation, by centrifugation in cesium chloride-propidium iodide, and by electron microscopy. It was found to consist of a majority of covalently closed circular DNA molecules. Length measurements of a few relaxed circular molecules indicate a molecular weight of these similar to that previously found for mature SPO2DNA. Attempts to isolate similar covalently closed circular phage DNA from induced bacteria lysogenic for SPO2 phage with a functional DNA polymerase gene were unsuccessful. The gene order in mature and prophage SPO2 was determined by rescue of single and double markers from the respective type of DNA. The data obtained show that prophage DNA is (genetically) permuted relative to mature DNA. The phage attachment site is suggested to be located between genes I and J.

Bacillus subtilis↗
PubMed1974

Protease-sensitive transfection of Bacillus subtilis with bacteriophage GA-1 DNA: a probable case of heterologous transfection.

The host bacterium of bacteriophage GA-1, Bacillus sp. G1R, was compared with respect to its taxonomic relationship to Bacillus subtilis, B. licheniformis, and B. pumilis. The physiological-biochemical properties of Bacillus sp. G1R are equal to those of B. licheniformis, but the thermal denaturation midpoint of G1R DNA differs by 3 C and the buoyant density by 0.005 g/cm(3) from that of B. licheniformis. Transformation with G1R donor DNA was neither observed in B. licheniformis nor in B. subtilis-competent recipients. Bacteriophage GA-1 shows neither infectivity on B. licheniformis nor on B. subtilis. However, infection of competent B. subtilis cultures with phenol-extracted GA-1 DNA results in the production of infective GA-1 particles. The transfecting activity of GA-1 DNA is destroyed by treatment with proteolytic enzymes. Resistance of transfecting DNA to inactivation by trypsin develops earlier than that to inactivation by DNase. Protease-treated GA-1 DNA competes with transforming DNA to approximately the same extent as does untreated GA-1 DNA, suggesting that uptake of GA-1 DNA is not affected by protease treatment. CsCl density gradient centrifugation reveals that the density of trypsinized GA-1 DNA is 0.004 g/cm(3) greater than that of untreated DNA.

Bacillus↗
PubMed1974

Induction of prophage SPO2 in Bacillus subtilis by 6-(para)-hydroxyphenylazouracil.

DNA replication in Bacillus subtilis is reversibly inhibited by 6-(para)-hydroxyphenylazouracil (HpUra) (1971), whereas replication of temperature phage SPO2 is not affected by the drug. Experiments are presented which show that HpUra will induce bacteria lysogenic for SPO2. Also, prophage phi105, which is sensitive to the drug, is induced by HpUra. Induction of SPO2 lysogenics in the presence of HpUra gives selective synthesis of SPO2 DNA.

Azo Compounds↗
PubMed1974

Induction of prophage SPO2 in Bacillus subtilis: prophage excision in the absence of bacterial or bacteriophage DNA synthesis.

Bacillus subtilis lysogenic for SPO2 wild type was induced under conditions preventing synthesis of both bacterial and phage DNA. The infectivity of phage DNA in transfection is strongly decreased under these conditions, whereas the activity of single phage genes as measured by marker rescue with superinfecting phage is unaffected. DNA from induced cells was sedimented in neutral sucrose gradients. After induction, phage DNA was detected at a position in the gradients, which was different from the bulk of the bacterial DNA, corresponding to linear double-stranded DNA of about 25 x 10(6) daltons. Similar results were obtained with bacteria lysogenic for a SPO2 prophage carrying a DNA-negative mutation. No separation of phage and bacterial DNA activity was detected when chloramphenicol was present during the induction period. These experiments show that prophage SPO2 can excise from the bacterial chromosome without previous replication.

Azo Compounds↗
PubMed1971

In vitro excision-repair of ultraviolet-irradiated transforming DNA from Bacillus subtilis.

The biological activity of UV-inactivated Bacillus subtilis DNA is partly restored after incubation with a UV-specific endonuclease from Micrococcus lutens in conjunction with DNA polymerase and DNA ligase, both isolated from Escherichia coli. The restored activity is not further increased by photoreactivation. Pyrimidine dimers are specifically liberated when irradiated DNA is exposed to the three enzymes. None of these effects is observed when pancreatic DNase is used instead of UV-specific endonuclease.

Bacillus subtilis↗
PubMedDate not supplied

Host-cell reactivation of cis-diamminedichloroplatinum(II)-treated SV40 DNA in normal human, Fanconi anaemia and xeroderma pigmentosum fibroblasts.

Cell survival after treatment with cis-diamminedichloroplatinum(II) [cis-Pt(II)] and host-cell reactivation of cis-Pt(II)-treated SV40 DNA were investigated using two Fanconi anaemia, one xeroderma pigmentosum of complementation group A, and three normal human control fibroblast cell strains. The Fanconi anaemia and xeroderma pigmentosum cell strains showed an increased sensitivity to the cytotoxic action of cis-Pt(II) treatment, suggesting a deficiency in the repair pathway of cis-Pt(II)-induced damage. In addition, the survival of cis-Pt(II)-treated SV40 DNA was about 2-fold lower in xeroderma pigmentosum cells than in control cells. No difference in viral DNA survival was found between Fanconi anaemia and control cells, although the Fanconi anaemia cells were more sensitive to the cytotoxic action of treatment with cis-Pt(II) than the xeroderma pigmentosum cells in the clonogenic cell survival assay.

Cell Line↗
PubMedDate not supplied

Differential response to mitomycin-C- and cis-diamminedichloroplatinum(II)-induced damage in normal human fibroblasts during confluent holding.

Confluent cultures of normal human fibroblasts were treated with the chemotherapeutic agents, mitomycin C (MMC) and cis-diamminedichloroplatinum(II) (cis-Pt(II]. This treatment induced a decrease in clonogenic cell survival. Recovery of the cytotoxic effect was observed in the case of cis-Pt(II)-treated cultures maintained at confluence for 1-5 days. No such recovery was observed after treatment with MMC. These data suggest that contrary to potential lethal damage induced by cis-Pt(II) which is repaired in confluent cells, DNA damage induced by MMC is not repaired in confluent cells.

Cell Cycle↗
PubMedDate not supplied

Somatic mosaicism in Fanconi anemia: molecular basis and clinical significance.

Approximately 25% of patients with Fanconi anemia (FA) have evidence of spontaneously occurring mosaicism as manifest by the presence of two subpopulations of lymphocytes, one of which is hypersensitive to cross-linking agents (e.g. mitomycin C) while the other behaves normally in response to these agents. The molecular basis of this phenotypic reversion has not yet been determined. We have investigated 8 FA patients with evidence of mosaicism. Epstein-Barr virus-immortalized lymphoblastoid cell lines established from these patients exhibited an IC50 for mitomycin C of 25 to > 100 nM compared to a mean of 2 +/- 2 nM for 20 nonmosaic FA patients and 49 +/- 11 nM for 8 healthy controls. In 3 patients who were compound heterozygotes for pathogenic FAC gene mutations the molecular mechanism of the mosaicism was investigated by haplotype analysis. The results indicated that an intragenic mitotic recombination must have occurred leading to a segregation of a wild-type allele in the reverted cells and suggested two patterns of recombination. In 1 patient a single intragenic crossover between the maternally and paternally inherited mutations occurred associated with markers located distally to the FAC gene; in the other 2 patients (sibs) the mechanism appears to have been gene conversion resulting in segregants which have lost one pathogenic mutation. In 6 of the 8 patients the hematological symptoms were relatively mild despite an age range of 9-30 years.

Adolescent↗