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Biomedical subjects

M Chorazy

Publications and source records attributed to M Chorazy.

At least 55 records · Page 3Linked to original sources

DNA adducts in humans related to occupational and environmental exposure to aromatic compounds.

White blood cell DNA adducts were measured in coke workers, local controls and countryside controls using the 32P-postlabelling technique and immunoassay. The methods detected aromatic adducts, including those formed by polycyclic aromatic hydrocarbons. Coke workers are heavily exposed to aromatic compounds, which are also emitted in large amounts into the environment. The two techniques detected a large difference in adduct levels between the coke workers and the countryside controls. The adduct levels in the local controls were substantially higher than those in the countryside controls. As occupational exposure did not account for such a difference, the data suggest that the source of aromatic adducts in local controls is environmental pollution.

Adult↗

Mutagenic activity of complex air pollutants in Silesia.

Continuous monitoring of air over the highly industrialized region of Silesia, Poland, shows high pollution with free sedimenting particulate matter, gaseous compounds and metals. Partial chemical analysis of extracts from airborne particulate material revealed over a hundred polycyclic aromatic hydrocarbons (PAHs); 15 major PAHs were evaluated quantitatively at 20 measuring points during summer and winter periods. Both direct and indirect mutagenic activity in extracts of particulate material was observed, with seasonal variations in activity. The direct mutagenic activity was higher in winter samples than in summer ones. Summer samples exhibited high mutagenic activity after metabolic activation of extracts.

Air Pollutants↗

Activation of the glucose-regulated gene (grp78) in regenerating rat liver is nonspecific and is related to acute phase response.

The expression pattern of the hsp70 gene family during regeneration or rat liver has been investigated. Northern blots were prepared from total RNA isolated from livers at 0 h (control), 12 h (end of prereplication phase), 24 h (maximum of DNA synthesis) and 36 h (postmitotic phase) after partial hepatectomy. Blots were hybridized with probes specific for the hsp70 (heat-inducible), hsc70 (constitutively expressed), hst70 (testis-specific) and grp78 (glucose-regulated) gene. No hsp70 and hst70 gene transcripts have been detected at any time point investigated, and only a low increase of the hsc70 mRNA level has been observed 24 h after surgery. In contrast, a significant accumulation of the transcript coded by the grp78 gene has been detected in liver remnant 12 and 24 h after partial hepatectomy. However, we observed a comparable activation of this gene in livers of sham-operated rats or in rats injected with turpentine to cause sterile inflammation. Our results indicate that the activation of the grp78 gene in liver of wounded rats (partial hepatectomy or sham operation) is presumably a part of acute-phase response.

Acute-Phase Reaction↗

Expression of "cell-cycle-dependent" genes in regenerating rat liver.

The expression of genes coding for the ATP/ADP translocase, calcyclin, ornithine decarboxylase, vimentin, proto-onc genes p53 and c-Ha-ras1 and also for two genes JE and KC with as yet unknown function was studied during regeneration of rat liver. Genes highly induced were: JE (2-8 h of regeneration), ATP/ADP translocase (8-18 h), c-Ha-ras-1 (6-48 h) and p53 (6-12 h). Vimentin and KC gene transcripts were not detectable in the first 48 h of liver regeneration, whereas ornithine decarboxylase and calcyclin gene transcripts were present at constant levels. Our findings extend the list of genes expressed at the early stages of liver regeneration.

Animals↗

[Whole blood and plasma viscosity and erythrocyte aggregation in power plant repairmen].

Forty-nine workers employed at power plants repairs underwent examinations and tests of: circulatory system, whole blood and plasma viscosity, red cell aggregation, concentration and electrophoretic picture of serum proteins, levels of glucose in blood and cholesterol and beta lipoproteins in serum. Ten per cent of the test workers exhibited slight deviations of the circulatory system. More pronounced changes, as compared to controls, were found in rheological factors: corrected blood and plasma viscosity and red cell aggregation were increased but hematocrit was decreased. Biochemical investigations showed a fall in serum total proteins and albumins and a rise in serum cholesterol and beta lipoproteins.

Adult↗

Association of SV40 DNA sequences with nuclear matrix in SV40 transformed hamster fibroblasts.

Nuclear matrices were isolated by the high-salt, non-ionic detergent method from SV40-transformed hamster fibroblasts (TSV5 cell line), and from hamster tumours derived from these cells. DNA isolated from matrices and total nuclei was hybridized with nick-translated SV40 DNA. The enrichment of matrix DNA with SV40 DNA sequences was observed in all five experiments with matrix DNA of TSV5 cells but only in five out of nine matrix DNA isolated from tumour cells.

Animals↗

Sequence rearrangements and genome instability. A possible step in carcinogenesis.

A substantial part of the mammalian genome is composed of sequences that do not contain structural genes. These sequences may constitute the major target for physical, chemical and biological DNA-damaging agents and can be involved in carcinogenesis. DNA-damaging agents contribute to the instability of the genome by introducing recombination-prone sites at DNA; these agents lead to extensive chromosomal lesions and rearrangements of genes and their regulatory sequences. Movable sequences that exist and operate in certain bacteria, yeast, and the fruit fly are responsible for sequence rearrangements and contribute to the majority of mutations. Their presence and role in higher animals is not well established. Extensive chromosomal rearrangements were identified in numerous malignancies in man and animals and definitely seem to represent a characteristic of malignancy. Vast chromosomal damage and sequence reshuffling may be of no less importance in the malignant transformation than the point mutation of a particular gene.

Animals↗

Use of adenosine 5'-0-(2-thiotriphosphate) for revealing of newly initiated transcripts in isolated rat liver nuclei.

Initiation of DNA-dependent RNA synthesis in isolated rat liver nuclei was studied with adenosine 5'-0-(2-thiotriphosphate), (beta-S-ATP), as a precursor. The newly made RNA labelled with sulfur at 5'-triphosphate termini (thio-RNA) was isolated by affinity chromatography on a mercury-agarose column. Sulfur label can be removed from thio-RNA by digestion with phosphodiesterase I and nucleotide pyrophosphatase. Gel electrophoresis revealed that thio-RNA synthesized during 30 min was composed of 4S-35S molecules with three prevailing classes grouped around 4S-5S, 16S and approximately 35S. Differential sensitivity of the thio-RNA classes to low (1 microgram/ml) and high (200 micrograms/ml) concentrations of alpha-amanitin disclosed that beta-S-ATP was used for initiation of transcription by all three classes of RNA polymerases, and that thio-RNA included molecules as large as 18S initiated by RNA polymerase II. Thio-RNA resistant even to high doses of alpha-amanitin represents probably a product of RNA polymerase I which was initiated and elongated up to 35S.

Adenosine Triphosphate↗

Complexity of liver mRNA from normal and thioacetamide-treated rats.

The complexity and diversity of polysomal poly(A)-containing RNA (mRNA) isolated from livers of normal and thioacetamide (TAA)-treated rats were compared by mRNA/complementary DNA hybridization technique. Three kinetic components (frequency classes) representing in normal mRNA about: I-34, II-32 and III-34% of RNA, apparently contained about 3, 60 and 3400 different sequences of 1 kb each, respectively. The corresponding values for mRNA from TAA-treated rats were about: I-24, II-36, and III-40%, comprising about 1, 30 and 3200 different sequences. It appeared that abundant mRNA sequences (from components I and II) may be 2-5 times more frequently represented in mRNA from TAA-treated than from normal rats. About 15% of mRNA sequences in TAA-treated rats were apparently transcribed from repetitive DNA reassociated to a Cot of 100. The results suggested that thioacetamide, a potent hepatocarcinogen, modulates the transcription or post-transcription regulatory steps of a few selected mRNA species, leading to their accumulation in the cell.

Acetamides↗

Metrizamide gradient centrifugation of histone-DNA complexes.

Mouse DNA was complexed with different combinations of histones. Most of these complexes were separated in metrizamide gradient into two fractions--heavy and light. At the protein: DNA ratio of 0.8 a complex of DNA with five histones contained 60% of DNA in the heavy fraction whereas in the absence of histone H1, this fraction contained only 40% of DNA. Complexes of DNA with the H2A + H2B histone pair banded in metrizamide as one, light fraction at the density of 1.140 g/cm3. DNA reconstituted with the H3 + H4 histone pair formed in metrizamide two peaks of 1.240 g/cm3 and 1.140 g/cm3. Among complexes of DNA with single histones H2A, H2B, H3 and H4 only the complex DNA-H4 formed a component having in metrizamide a density of 1.200 g/cm3, similar to the density of purified chromatin.

Animals↗

Separation of mercury substituted RNA synthesized in isolated rat liver nuclei.

The population of RNA molecules synthesized in isolated rat liver nuclei in vitro in the presence of [3H]CTP and Hg-UTP was successfully fractionated into at least two subfractions containing various proportions of mercury label. Fractionation was achieved either by step-wise chromatography of Hg-RNA on thiopropyl-Sepharose columns or by density gradient centrifugation in metrizamide. The fraction of RNA heavily labeled with Hg-UTP was composed mainly of 4--18S RNA and contained virtually all radioactivity derived from [gamma-32P]ATP or [gamma-32P]GTP. The slightly mercurated RNA fraction consisted mainly of longer RNA molecules (12- greater than 28S) and was not labeled with [gamma-32P]ATP or [gamma-32P]GTP. Labeling with gamma-32P nucleoside triphosphates was sensitive both to rifamycin AF/013 and heparin whereas labeling with [3H]CTP was fully resistant to the inhibitors and showed sensitivity to low doses of alpha-amanitin. We assume that the observed subpopulation of heavily mercurated RNAs consists of RNA molecules initiated in vitro.

Animals↗

Mutagenic activity of some 9-aminoalkyl acridine derivatives on S. typhimurium.

The mutagenic potential of 9-(3'-dimethylaminopropylamino)-acridine and of its 1-nitro and 2-nitro derivatives was investigated by using histidine-requiring mutants of Salmonella typhimurium. The 9-(3'-dimethylaminopropylamino)-acridine exhibited a weak mutagenic activity only on one of the S. typhimurium tester strains, TA1537. The 1-nitro derivative induced mutations with high frequency in strains TA1537, TA1538 and TA98, whereas the 2-nitro derivative was substantially more mutagenic than the parent compound but it was much less mutagenic than the 1-nitro derivative. Pre-mutational damages made by the 1-nitro derivative were repaired by the uvrB gene-repair system, whereas those caused by the 2-nitro derivative could not be repaired by this system. Both the 1-nitro and 2-nitro derivatives induced some mutations in the base-pair substitution strain TA100 carrying a plasmid. The frequency of the his+ mutation induced both by 1-nitro and by the 2-nitro derivatives in strain TA101 lacking a nitro reductase was lower. These results emphasize the involvement of the nitro group in the interaction of acridine derivatives with the bacterial genome.

Acridines↗

Comparison of cytoplasmic RNA species from rat liver and Morris hepatoma 5123D.

1. In a highly differentiated Morris hepatoma 5123D the fraction of repetitive, cytoplasmic poly(A)-containing RNA hybridizing with DNA to the Cot values below 10(2) mol X sec/l is present in a higher proportion than in normal rat liver. 2. Unique sequences of cytoplasmic RNA containing poly(A) both in Morris hepatoma and normal rat liver exhibit similar hybridization kinetics. 3. No sequence differences in cytoplasmic poly(A)-free RNA between Morris hepatoma 5123D and normal rat liver were found using hybridization-competition technique.

Animals↗