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Biomedical subjects

G Obe

Publications and source records attributed to G Obe.

At least 145 records · Page 8Linked to original sources
PubMed1980

Possible mutagenicity of the psychoactive phenothiazine derivative perazine in vivo and in vitro.

Human lymphocyte cultures from 55 schizophrenic subjects and one manic-depressive subject being treated with the phenothiazine derivative perazine and with other drugs were analyzed with respect to chromosomal damage. The frequency of exchange-type aberrations in these subjects was more than double that in clinically normal control subjects. No correlation was detectable between the aberration frequency and sex, age, smoking and drinking habits, and treatment conditions. It is possible that the elevation of the chromosomal aberration frequency is due to perazine. In vitro studies with perazine and two main metabolites (desmethylperazine and perazine sulfoxide) with human lymphocytes and CHO cells with and without metabolic activation by liver microsomes gave negative results with respect to the induction of sister chromatid exchanges. Possible differences in the metabolism of perazine in vivo and in vitro are discussed.

Adolescent↗
PubMed1980

Studies on the influence of liquid holding in con-A stimulated human peripheral blood lymphocytes on mitosis and X-ray induced chromosome aberrations.

A method suitable for performance of liquid-holding (LH) experiments with human lymphocytes in vitro is described. The lymphocytes are stimulated with concanavalin A (Con A) and after washing off the Con A with a sugar-containing medium are liquid-held in Con A-free medium for different times, after which they are restimulated with Con A. The BUdR-labeling method was used to determine the proportion of first-, second-, and third-division cells. With this system we were able to show that the frequencies of X-ray-induced chromosomal aberrations are not influenced by liquid holding, supporting the idea that these aberrations are fixed shortly after irradiation by misrepair. This sytem may prove useful for investigation of specific problems in mutagenicity research, especially those involving mutagens, which induce delayed formation of chromosome aberrations.

Cell Cycle↗
PubMed1980

Comparison between inactivated Sendai virus, polyethylene glycol and Tween 80 as permeabilizing agents for introduction of neurospora endonuclease into X-irradiated cells.

Inactivated Sendai virus, polyethylene glycol and Tween 80 were employed as agents to make X-irradiated CHO cells permeable for Neurospora endonuclease, in studies designed to evaluate the influence of this enzyme on the frequencies of X-ray-induced chromosome aberrations. Polyethylene glycol and Tween 80 were found not to be very efficient in making cells permeable. Besides, polyethylene glycol was found to increase the frequencies of X-ray-induced chromosomal aberrations.

Animals↗
PubMed1980

Molecular mechanisms involved in the production of chromosomal aberrations. II. Utilization of Neurospora endonuclease for the study of aberration production by X-rays in G1 and G2 stages of the cell cycle.

Chinese hamster ovary cells (CHO) were X-irradiated in G1 and G2 stages of the cell cycle and subsequently Neurospora endonuclease (NE) (E.C.3.1.4), an enzyme which is specific in cleaving single-stranded DNA, was introduced into the cells, after making the cells permeable by treatment with inactivated Sendai virus. With this treatment all classes of X-ray-induced chromatid aberrations increased in G2 cells, whereas in G1 cells an increase in chromosome type of aberrations was found, associated with a profound induction of chromatid type of aberrations as well. Duration of the availability of single-strand gaps for the action of NE has been studied in G2 cells following X-irradiation and the influence of different parts of the G2 stage on the type and frequencies of chromatid aberrations was discerned. While the increase in chromosome type of aberrations by NE in X-irradiated G1 cells has been interpreted as due to the conversion of DNA single-strand breaks or gaps to double-strand breaks by NE, the induction of chromatid aberrations in G1 has been assumed to be due to conversion of some of the damaged bases into strand breaks by NE. Biochemical evidence is presented for the conversion by NE of DNA single-strand breaks induced by X-rays into double-strand breaks using neutral sucrose gradient centrifugation.

Animals↗
PubMed1980

Trenimon-induced SCEs and structural chromosomal aberrations in early- and late-dividing lymphocytes.

In cultures of human peripheral lymphocytes the frequencies of Trenimon-induced SCEs in second post-treatment metaphases and of structural chromosomal aberrations in first, second and third post-treatment metaphases were clearly lower at late as compared with early fixation times. These results, which are discussed, indicate that T cells (early dividing) are more sensitive with respect to the induction of SCEs and structural chromosomal aberrations by Trenimon as compared with B cells (late dividing).

Adult↗
PubMed1980

Use of the 5-bromodeoxyuridine-labelling technique for exploring mechanisms involved in the formation of chromosomal aberrations.

Synchronized G1 CHO cells with chromosomes of TB or TT constitution were irradiated with X-rays, short-wave UV and long-wave UV. The types and frequencies of chromosomal aberrations observed in the ensuing mitosis were studied. X-Rays induced predominantly chromosome types of aberration in chromosomes of TT constitution, whereas both chromosome- and chromatid-types of aberration were induced in cells with chromosomes of TB constitution. Short-wave UV induced only chromatid types of aberration in cells containing chromosomes of TT constitution, but both chromosome and chromatid types of aberration in cells with chromosomes of TB constitution. Long-wave UV induced chromosome and chromatid types of aberration in cells with chromosomes of TB constitution and no aberrations in cells containing chromosomes of TT constitution. Long-wave UV-irradiation of cells containing chromosomes of TB constitution increases the frequencies of SCEs. The relationship between chromosome constitution (TT or TB), the type of lesions induced by the 3 different agents employed, and the types of chromosomal aberration induced are discussed.

Animals↗
PubMed1980

Chromosomal aberrations in peripheral lymphocytes of alcoholics.

The frequencies of exchange-type aberrations found in peripheral lymphocytes of alcoholics were analysed in relation to age, sex, duration of alcohol dependency, treatment with antabuse and smoking habit. The statistical analyses were performed by the non-parametric Mann-Whitney U test and the Kruskal-Wallis 1-way analysis of variance, both at a level of significance of P = 0.05. There was no dependency on age or sex. The chromatid exchange frequencies and the total of all exchanges were positively correlated with the duration of the dependency on alcohol and with smoking habit. Treatment with antabuse did not lead to an additional elevation of the frequency of exchange-type aberrations.

Adolescent↗
PubMed1980

Is lithium mutagenic in man?

Peripheral blood lymphocytes of 77 patients under lithium-therapy were analyzed with respect to structural chromosomal aberrations. As compared to controls not treated with lithium, no elevation of the frequencies of chromosomal aberrations was found in the patients. Comparable investigations may lead to erroneous conclusions if the higher X-ray load of psychiatric patients is not considered.

Adult↗
PubMed1979

Sister chromatid exchanges in human leukocyte chromosomes: spontaneous and induced frequencies in early- and late-proliferating cells in vitro.

Human leukocyte cultures were pulse-treated with the trifunctional alkylating mutagen trenimon in a final concentration of 10(-7) M for 15--20 h after culture start, i.e., in the G1 phase of the cell cycle. At 24 h after culture start bromodeoxyuridine (BUdR) was added to the trenimon-treated cultures and to several untreated cultures running in parallel. The series treated with BUdR only and the series treated with BUdR+trenimon were each used to prepare two cultures at different culture times. Mitoses were collected during consecutive intervals of 12 h from 30 h up to 102 h after culture initiation by colcemid. For all preparation times (42 h, 54 h, 66 h, 78 h, 90 h, and 102 h) the frequencies of first, second, and third and further mitoses were determined in the BUdR- and in the BUdR+trenimon-treated series. In the trenimon-treated series a clear cell cycle delay was detected as compared with the normal distribution of different types of mitoses found in series treated with BUdR only. Spontaneous and trenimon-induced sister chromatid exchange (SCE) frequencies were determined in second mitoses occurring at 66 h, 78 h, 90 h, and 102 h after culture start. For all these preparation times about six SCE per metaphase were consistently found in BUdR-treated, and about 19 SCE per metaphase in BUdR+-trenimon-treated series, indicating a homogeneous sensitivity of early- and late-proliferating cells with respect to the induction of SCE.

Bromodeoxyuridine↗
PubMed1979

Mutagenic, cancerogenic and teratogenic effects of alcohol.

Alcohol is mutagenic, cancerogenic and teratogenic in man. Ethanol is mutagenic via its first metabolite, acetaldehyde. This is substantiated by the findings that acetaldehyde induces chromosomal aberrations, sister-chromatid exchanges and cross-links between DNA strands. Methanol, a contaminant of many alcoholic beverages, is also mutagenic via its metabolite, formaldehyde. In addition, different indirect pathways may lead to mutations by alcohol. The cancerogenic activity of alcohol remains unverified by modern standard carcinogenicity tests. Ethanol and other alcohols, as well as aldehydes, inhibit RNA synthesis in cells and in cell-free transcriptional systems. A reduction of cellular RNA synthesis may play an important role in the mutagenic, carcinogenic and teratogenic activity of alcohol.

Acetaldehyde↗
PubMed1979

Trenimon: biochemical, physiological and genetic effects on cells and organisms.

The trifunctional alkylating mutagen Trenimon interferes with the genetic material of a variety of organisms and test systems with respect to the induction of point and chromosomal mutations, sister-chromatid exchanges, recombination phenomena and phage induction. Beneath these mutagenic effects several biochemical and cell physiological aspects have been investigated. In this review we discuss chemical and cell physiological effects of Trenimon, aspects of cancer therapy with Trenimon and genetic effects induced by Trenimon. The available data on mutagenic effects of Trenimon are presented according to organisms or test systems. A short discussion on a possible genetic load by therapy with Trenimon in man concludes this review. DNA damage, especially the induction of cross-linkings, seems to represent the common reason for most of the described effects of Trenimon on cells and organisms.

Animals↗
PubMed1979

The influence of ethanol treatment of cytogenetic effects in bone marrow cells of Chinese hamsters by cyclophosphamide, aflatoxin B1 and patulin.

Chromosomes were investigated from the bone marrow of Chinese hamsters which received 10% (v/v) ethanol as the only liquid supply for a period of 9 weeks. At the end of the ethanol drinking period 1 group of animals received 2 oral doses of 80 mg/kg cyclophosphamide (CP), a second group received 2 oral doses of 25 mg/kg aflatoxin B1 (AFB1), a third group 2 oral doses of 20 mg/kg patulin (PA). The 2 applications were separated by 24 h. The intake of ethanol had no effect on the bone marrow chromosomes, and had no potentiating effect on CP induced aberrations. 9 weeks consumption of 10% (v/v) ethanol revealed likewise no influence on the frequencies of chromosomal aberrations induced by the indirect mutagen AFB1. However, the rate of chromosomal aberrations induced by the direct mutagen PA was clearly suppressed in ethanol drinking animals.

Aflatoxins↗
PubMed1979

Characterization of feline whole-blood cultures and determination of the frequency of radiation-induced dicentrics in human and feline lymphocytes.

The Ham's F-10 and PHA culture system was applied to whole feline blood and cell-cycle characteristics such as DNA synthesis and mitotic indices were studied. The results are comparable to those obtained from human whole-blood cultures. The yields of dicentrics were also determined in lymphocytes from X-irradiated human and feline blood. The ratio between the experimental yields of dicentrics in human as compared to feline lymphocytes was 1:0.27.

Animals↗
PubMed1978

No elevation of exchange type aberrations in lymphocytes of children with alcohol embryopathy.

The lymphocyte chromosomes from 23 children with the 'fetal alcohol syndrome' or 'alcohol embryopathy' (AE) were analyzed with respect to exchange type aberrations. These aberrations were not more frequent in AE than in controls. The possibility that AE results from unspecific suppression of RNA and consequently of protein synthesis in the developing embryo is discussed.

Abnormalities, Multiple↗
PubMed1978

Chromosome analyses in man in the course of chemoprophylaxis against tuberculosis and of antituberculosis chemotherapy with isoniazid.

Cytogenetic analyses were carried out in lymphocytes of 37 persons before and during a primary chemoprophylaxis or a preventive chemotherapy with isoniazid as well as of 30 patients suffering from active pulmonary tuberculosis before and during a chemotherapy with isoniazid in combination with two other antimycobacterial drugs. The results of the four participating research groups consistently reveal no indication for a chromosome damaging activity of isoniazid, of its metabolites in the human organism and of the administered drug regimens.

Adolescent↗
PubMed1978

Chromosomal aberrations in heavy smokers.

Lymphocyte chromosomes from 20 heavy smokers were analyzed from 48-h whole blood cultures for the frequency of dicentric chromosomes, ring chromosomes, and chromatid translocations. Compared to controls, these exchange type aberrations occurred more frequently in the smokers.

Adult↗