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B Beek

Publications and source records attributed to B Beek.

At least 19 recordsLinked to original sources
PubMed1986

Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1.

Three animal species used in in vivo mutagenicity testing--rats, mice and Chinese hamsters--were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE-inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathione conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an "inappropriate" test species may lead to a false negative judgment on the genotoxic potential of a test compound.

Aflatoxin B1↗
PubMed1986

Species differences in mutagenicity testing. II. Sister-chromatid exchange and micronucleus induction in rats, mice and Chinese hamsters treated with cyclophosphamide.

Comparative investigations of sister-chromatid exchange (SCE) and micronucleus induction in the bone marrow of rats, mice and Chinese hamsters with the cytostatic alkylating mutagen cyclophosphamide (CP) revealed remarkable species differences in their mutagenic responses. With both test systems the sensitivities of the three species can be ranked into the order rat greater than mouse greater than Chinese hamster. More explicit results were obtained with the SCE test than with the micronucleus test within the same dose range. This may be due to the influence of species-related differences in the cytotoxic response to CP in the micronucleus test. These results show that clearly different mutagenic responses in different test species may be obtained in standard assays even with a compound which is metabolized in a very similar manner in all animal species.

Animals↗
PubMed1983

Fragile sites in chromosomes: possible model for the study of spontaneous chromosome breakage.

The tissue culture condition that is required for the type of chromosome breakage seen at most fragile sites, namely, the absence of folic acid and thymidine in the medium, greatly enhanced micronucleus formation in proliferating lymphocyte cultures from normal individuals. This suggests that chromosome breakage at fragile sites and the apparently spontaneous damage that gives rise to micronuclei are controlled by the same mechanism.

Adolescent↗
PubMed1982

Induction of sister-chromatid exchanges, cell-cycle delay and chromosomal aberrations by human urine concentrates.

Human urine concentrates, prepared with the use of XAD-2 resin, are shown to be potent inducers of sister-chromatid exchanges, and especially of chromosomal damage and cell-cycle delay in Chinese hamster ovary cells. No indications for differences in mutagenic activity were found between concentrates prepared from the urine of smokers, non-smokers or patients with alcoholic cirrhosis of the liver. These effects were obtained without metabolic activation in vitro. Experiments including variations in preparative procedures indicate that a quick saturation of the resin by non-polar compounds from human urine may lead to an underestimation of the amount of mutagenic substances in a given urine sample.

Animals↗
PubMed1981

Cell proliferation and chromosomal damage in human leukocytes: dicentrics and premature chromosome condensations in first, second, and third mitoses after X-irradiation.

The frequencies of dicentric chromosomes and of partial premature chromosome condensation (PCC) in definitely first, second, or third mitoses after X-irradiation of human leukocytes, as determined with a bromodeoxyuridine (BUdR)/ Giemsa labeling technique, were investigated. The results show that practically no PCCs occur in first mitoses after irradiation and culture start in contrast to second or third ones. The frequencies of dicentrics from first to second, as well as from second to third mitoses after irradiation decline by about 50% for each division step.

Bromodeoxyuridine↗
PubMed1981

BUdR-giemsa labeling and satellite association in human leukocytes.

Satellite associations were analysed in differentially stained human leukocyte chromosomes, obtained from four patients with Down's syndrome and four normal probands. A particular type of close association between two acrocentrics, showing a non-random arrangement of sister chromatids in a concordant dark-to-dark and light-to-light alignment, was found to be more common in patients with Down's syndrome compared with the normal controls. Apart from this particular type of association, sister chromatids are randomly arranged in satellite associations between two acrocentrics in both groups of probands. Considerable differences in the mean frequencies of satellite associations between first and second metaphases of the same individual were found in some probands of both groups of individuals. Since a high degree of inter-individual variability in the proliferative response of human leukocytes in culture is well established, the use of BUdR-Giemsa labeling for comparative analysis of satellite association frequencies is suggested.

Azure Stains↗
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

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↗
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↗
PubMed1977

Differential chromosomal radiosensitivity within the first G1-phase of the cell cycle of early-dividing human leukocytes in vitro after stimulation with PHA.

Human leukocyte cultures were irradiated with 200 RX-rays before the addition of phytohemagglutinin (PHA) in the Go-stage and at different times up to 25 h within the first G1-phase of the cell cyle after the addition of PHA. The results of the analysis of chromosomal aberrations show that the frequencies of dicentric chromosomes increase significantly when leukocytes leave the Go-stage, reaching a miximum yield of aberrations about halfway through the first G1-phase. After that, toward the end of the G1-phase, the frequencies of dicentric chromosomes decrease again to a level similar to that found in the Go-stage. Different possible explanations for the differential chromosomal radiosensitivity of human leukocytes within the first post-stimulation G1-phase are discussed.

Chromosome Aberrations↗
PubMed1976

The human leukocyte test system. X. higher sensitivity to X-irradiation in the G0 stage of the cell cycle of early as compared to late replicating cells.

Leukocyte cultures were set up with X-irradiated whole blood (200 R). Cells starting with their DNA synthesis between 25 and 35 h after cultureinitiation ("early replicating cells") were pulse-labeled with tritiated thymidine ([3H]TdR). Mitoses were collected with colcemid in adjacent intervals from 36 up to 72 h after culture initiation. At fixation times of 50, 56, 62, and 72 h enough mitoses for a determination of the frequencies of chromosomal aberrations (dicentric and ring chromosomes) were found. After that the preparations were processed for autoradiography. All mitoses analyzed for chromosomal aberrations were re-analyzed for labeling, and the frequencies of chromosomal aberrations in labeled (="late replicating cells") mitoses were compared. At all fixation times, higher frequencies of dicentric chromosomes were found in labeled as compared to unlabeled mitoses, indicating a higher sensitivity of early replicating cells to X-irradiation in the G0 stage of the cell cycle.

Chromosome Aberrations↗
PubMed1976

The human leukocyte test system. IX. DNA synthesis and mitoses in PHA-stimulated 2-day cultures set up with Eagle's mimimal essential medium (MEM).

In human leukocyte cultures set up with Eagle's MEM and stimulated with Difco's PHA M, DNA synthesis and mitotic indices were analyzed by means of 3(H)-thymidine autoradiography and cell counting from 23 up to 52 h after culture initiation. Considerable amounts of DNA synthesis and mitoses were found in this time span. This resembles the results found with Ham's F-10 medium. However, the DNA synthesis pattern and the distribution of mitotic indices a higher yield of asynchrony in Eagle's MEM as compared with Ham's F-10 cultures. Proportions of first, second, and third mitoses at 72 h culture time were determined with different methods.

Culture Media↗
PubMed1976

The human leukocyte test system. VIII. DNA synthesis and mitoses in 3-day cultures stimulated with pokeweed mitogen.

In human leukocyte cultures set up with Ham's F-10 medium and stimulated with pokeweed mitogen (PWM), DNA synthesis and mitotic indices were analyzed by means of (3H)TdR autoradiography and cell counting. The results show a very similar pattern of DNA synthesis and mitotic indices to that found in cultures set up with TC medium 199 and stimulated with phytohemagglutinin (Obe et al., 1975 a).

Chromosome Aberrations↗
PubMed1975

The human leulocyte test system. VII. Further investigations concerning micronucleus-derived premature chromosome condensation.

Premature chromosome condensation (PCC) from X-ray induced micronuclei shows a dose-effect relationship in human leukocytes in vitro. Preparations at different culture times without colcemide treatment reveal complex variations of the frequencies of micronuclei and PCC correlated with the fixation time. The positions of PCC patches in the metaphase plate and the frequencies of different PCC types (S and G2) ar independent on the X-ray dose. The latter indicates that the slowing down of the micronuclei in the cell cycle, which is the reason for the formation of PCC, may be an outcome rather of a regulatory phenomenon than of an unspecific physiological damage of the chromatin included in the micronuclei. This is especially evident from labeling experiments with tritiated thymidine, showing that the extent of asynchrony between main nuclei and micronuclei is independent on the X-ray dose. Labeling experiments with tritiated uridine reveal a X-ray dose dependent suppression of RNA synthesis in cells with main nuclei and micronuclei. THE S-phase nature of "pulverized" PCC patches could be verified by incorporation of tritiated thymidine in aound 50%. Staining of centromeric heterochromatin in micronuclei reveal a frequency of micronuclei with centromeric heterochromatin resembling the frequency of G2-phase PCC found in mitoses.

Cell Nucleus↗
PubMed1975

The human leukocyte test system. VI. The use of sister chromatid exchanges as possible indicators for mutagenic activities.

The trifunctional alkylating chemical mutagen trenimon increases the frequency of sister chromatid exchanges in human leukocyte chromosomes in vitro, as revealed by a BUdR-Giemsa method. Treatment with lead acetate exhibited negative results in this respect. The use of sister chromatid exchanges as possible indicators for mutagenic activities is discussed.

Cells, Cultured↗
PubMed1975

The human leukocyte test system. V. DNA synthesis and mitoses in PHA-stimulated 3-day cultures.

In human leukocyte cultures st up with TC medium 199,DNA synthesis and mitotic indices were analysed by means of 3H-thymidine autoradiography and cell counting. DNA synthesis starts at around 28 hrs. The frequencies of labelled cells rise slowly and reach a maximum of around 24%. The first mitoses appear at around 38 hrs but up to 49 hrs only very few mitoses can be seen. After that time the mitotic indices rise and reach values of up to 11% cultivation in the presence of BudR for 72 hrs and staining with Hoechst 33258 stain revealed that first, second and third mitoses occur together in the cultures at this time. Irradiation of whole blood and cultivation for 72 hrs leads to mitoses containing dicentric and ring chromosomes with and without fragments, to interphases with micronuclei, to premature chromosome condensations (PCC) and to polyploid mitoses indicating that at this time first and further mitoses are present.

Autoradiography↗