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Biomedical subjects

G Obe

Publications and source records attributed to G Obe.

At least 127 records · Page 7Linked to original sources
PubMed1982

Double-blind study on the effect of cigarette smoking on the chromosomes of human peripheral blood lymphocytes in vivo.

A double-blind study with 170 smokers and 124 non-smokers revealed a doubling of the frequencies of exchange-type aberrations in the peripheral blood lymphocytes of smokers as compared with non-smokers. Smokers (N = 24) had 1 SCE more per metaphase than non-smokers (N = 20), an effect that is significant but low when compared with the effect on structural chromosomal aberrations. These results show that structural chromosomal aberrations are better indicators of the genetical effects of low chronic exposures to mutagens in man than SCEs. The frequencies of micronuclei in 3-day lymphocyte cultures showed no differences in smokers (N = 95) and non-smokers (N = 39). Non-smokers (N = 99) had significantly higher frequencies of 2nd metaphases in 48-h cultures in vitro than smokers (N = 141), indicating an effect of smoking on the stimulation of lymphocytes by PHA in vitro.

Cells, Cultured↗
PubMed1982

Evaluation of radiation-induced chromosomal aberrations in human peripheral blood lymphocytes in vitro: result of an IAEA-coordinated programme.

The results of an IAEA coordinated programme on radiation induced chromosomal aberrations in human peripheral blood lymphocytes in vitro are presented. In a master experiment, a whole blood sample from one donor was irradiated with 200 R of X-rays. Different fixation times from 46 to 82 h were used. The progression of cells into mitosis was monitored by BrdUrd incorporation. 14 investigators took part in the scoring of chromosomal aberrations. The main conclusions of this study are: (1) The mean frequencies of aberrations changed with fixation time. (2) The number of cells scored as aberrant by different laboratories was very similar, but there was variability in the number of aberrations scored per aberrant cell. (3) The differences in the frequencies of aberrations between laboratories were minimal when the scoring was restricted to the first major peak of mitotic activity and sufficient cells were scored. It is concluded that using controlled experimentals conditions, human peripheral blood lymphocytes can effectively be used as a reliable biological dosimeter for absorbed radiation dose.

Argentina↗
PubMed1982

Mutagenic, teratogenic and pharmacokinetic properties of cyclophosphamide and some of its deuterated derivatives.

To elucidate which metabolic pathway leads to the ultimate mutagenic and teratogenic metabolite of cyclophosphamide (CPA), the mutagenicity in vitro as well as the teratogenicity in vivo and the pharmacokinetics of CPA and several deuterated analogs (5,5-d2-CPA, 4,4-d2-CPA and 4,4-6,6-d4-CPA) were compared. 5,5-d2-CPA was less mutagenic (isotope effects between 1.7 and 12.3 were found for sister-chromatid exchanges and structural chromosomal aberrations in CHO cells and in the Ames test) and less teratogenic (deuterium isotope effect between 2 and 3) than CPA and the other deuterated analogs. Because the concentrations of 5,5-d2-CPA in pregnant mice and their embryos were equal to or even exceeded those of CPA and the other deuterated analogs, a particular metabolic pathway involving a fission of the C-D or C-H bond on the C-5 rather than the parent drug must be responsible for the isotope effect observed. It had previously been shown (Cox et al., 1976) that the 5,5-d2-CPA has a decreased anti-tumor activity in vivo (isotope effect 7-13) which was accompanied by a decreased formation of phosphoramide mustard and acrolein in vitro (isotope effect 5.3). Our results suggest that phosphoramide mustard is an important proximate metabolite of CPA with regard to the mutagenicity and teratogenicity of the drug. These results show for the first time that labeling of drugs with stable isotopes offers a promising approach to the study of the mechanism of the mutagenic and teratogenic actions of drugs.

Animals↗
PubMed1982

Mutagens in human urine: test with human peripheral lymphocytes.

A test is described in which human peripheral blood is enclosed in dialysis bags and exposed to human urine. After the treatment, the blood is cultivated in the presence of bromodeoxyuridine, and metaphases are analyzed with respect to the frequencies of sister-chromatid exchanges (SCE). Urine from clinically healthy people and from epileptic patients on therapy with anti-epileptic drugs did not lead to an elevation of SCE frequencies. Urine from cancer patients treated with a multi-drug combination therapy including cyclophosphamide led to a significant increase in the frequencies of SCEs.

Adolescent↗
PubMed1981

Chromosomal aberrations in the peripheral lymphocytes of cancer patients treated with high-energy electrons and bleomycin.

5 patients with inoperable bronchogenic carcinomas on a weekly therapy with a low dose of bleomycin (BL) plus irradiation with high-energy electrons, were analysed cytogenetically by cultivating peripheral lymphocytes taken immediately before the BL treatments and some hours before the irradiations. For the induction of dicentric chromosomes, linear dose-effect relationships were found: 3 of the patients responded with similar dose-effect relationships. The other 2 were different: they were not comparable with those 3 or with each other. These results were unexpected because all 5 patients received similar types of treatment.

Aged↗
PubMed1981

Influence of chronic ethanol uptake and acute acetaldehyde treatment on the chromosomes of bone-marrow cells and peripheral lymphocytes of Chinese hamsters.

Chinese hamsters received 10% (v/v) ethanol as their only liquid supply during 46 weeks. At the end of the drinking period the rate of chromosomal aberrations was determined in cultured lymphocytes. The cultures were set up with the blood from the retro-orbital plexus. Bone-marrow metaphases of the same animals were analysed with regard to sister-chromatid exchanges (SCE) after implantation of BrdU tablets in vivo. No cytogenetic effects were found in either test system. Another group of Chinese hamsters received acetaldehyde at 0.01, 0.1 amd 0.5 mg/kg by i.p. injection, and bone-marrow metaphases were analysed with respect to SCE. The SCE frequencies were elevated by acetaldehyde at 0.5 mg/kg, but not by the lower doses.

Acetaldehyde↗
PubMed1981

Simultaneous exposure of Chinese hamsters to ethanol and cigarette smoke: cytogenetic aspects.

Chinese hamsters (Cricetulus griseus) were treated with ethanol, with cigarette smoke and with both. During the experimental period of 12 weeks a control group of animals (c) received water ad libitum, another water drinking group received a cigarette smoke treatment during the last 4 weeks (S). Another group received 20% (v/v) ethanol during the whole experimental period as the only liquid supply (E), and one group with the same ethanol treatment was simultaneously treated with cigarette smoke during the last 4 weeks of the experiment (ES). The investigation of bone marrow cells after 12 weeks with regard to chromosomal aberrations and sister chromatid exchanges revealed no effects. A high mitotic activity was found in the smoke treated groups.

Animals↗
PubMed1981

The use of rat liver perfusion to detect indirect mutagens/carcinogens in human leukocytes in vitro.

The rat liver perfusion technique in situ is used to metabolize the indirect mutagen cyclophosphamide (CP). Chromosomal damage (sister chromatid exchanges, chromatid translocations) caused by activated CP is investigated with human lymphocyte cultures in vitro, demonstrating dose- and time-effect relationships. Especially the treatment of human whole blood with CP perfusate of a recirculating perfusion system is recommended as a useful model system for the induction of chromosomal damage in peripheral lymphocytes in vivo in man.

Animals↗
PubMed1980

The effect of caffeine posttreatment on X-ray-induced chromosomal aberrations in human blood lymphocytes in vitro.

The potentiating effect of caffeine on X-ray-induced chromosomal aberrations in human blood lymphocytes has been investigated, with special reference to cell cycle stages (G0 and G2). Both quantitative and qualitative differences in the yield of chromosomal aberrations were detected in caffeine-posttreated cells, depending on the cell stage irradiated. The studies on caffeine potentiating effects on X-irradiated G0 lymphocytes from normal adults, newborns, Down syndrome patients, and an ataxia telangiectasia patient pointed to interindividual variations in the response to caffeine potentiation among normal probands and a very profound effect in ataxia cells.

Adult↗
PubMed1980

Methods for analysis of the mutagenicity of indirect mutagens/carcinogens in eukaryotic cells.

The review discusses the variety of methods for activation of indirect mutagens/carcinogens and testing them in cell cultures, especially in mammalian cell cultures. After the necessity for including metabolizing components in mutagenicity tests has been pointed out, the enzymes that transform foreign compounds metabolically, and the factors influencing them, are described. In the main section the various methods of activating indirect mutagens/carcinogens are presented. The methods of including in vivo metabolism in mutagenicity tests are: Analysis of cells from organisms contaminated with a chemical (III.l.a); body fluid-mediated mutagenesis (III.l.b); host-mediated assay (III.l.c). The following activation systems are suitable for including in vitro metabolism of test compounds in mutagenicity tests: Liver and lung perfusion (III.2.a.alpha); organ slices and homogenates (III.2.a.beta); subcellular fractions (III.2.a.gamma); cultivated cells (cell-mediated mutagenesis) (III.2.b); nonenzymatic activation systems (III.2.c). Finally the main factors that influence the metabolism of test substances are summarized. Two factors illustrate the mutagenicity tests with regard to the metabolism of mammalian livers and the methods of performing mutagenicity tests in man.

Animals↗
PubMed1980

Has diagnostic ultrasound mutagenic effects?

Chinese hamster ovary cells were treated with ultrasound from a fetal pulse detector (Eucotone, Siemens) operated at 10 mW/cm2 and 2.2 MHz. The frequencies of structural chromosomal aberrations and of sister chromatid exchanges were not increased by the treatment. There was no indication of single-strand breaks induced by ultrasound in the G2 phase of the cell cycle.

Animals↗