Increase In Chromosome Damage Research Articles

Cytogenetic effects in a group of traffic policemen in Cairo

The aim of this study was to evaluate the cytogenetic effects in humans exposed to automobile exhaust. The induction of chromosome damage was studied in an exposed group of 28 traffic policemen with exposure of over 10 years and a control group of 15 policemen trainers from the Faculty of Police. The percentage of chromosomal aberrations as well as the mean sister-chromatid exchanges were significantly higher among the traffic policemen than in the control group. The cause for this elevated chromosome damage is most likely due to their exposure to pollutants from automobile exhaust, however, the increase is not correlated with the blood lead level or the duration of employment. On the other hand, the increase in chromosome damage among the traffic policemen is enhanced further by smoking.

Chromosomal effects in lymphocytes of 400 kV-substation workers

In a previous study we found an increased rate of chromosomal aberrations in substation workers. To follow up this finding we in this study present data from 38 employees of electric power companies; 19 of the subjects worked with the repair and maintenance of circuit breakers and disconnectors in 400 kV-substations. The other 19 served as controls and were only exposed to normal environmental electromagnetic fields. Coded blood samples were sent to a laboratory for determination of the rate of chromosomal aberrations (CA), sister chromatid exchanges (SCE), and cells with micronuclei (MN). Compared to the control group the exposed men displayed a statistically significant increase in CA and cells with MN. No increase was found in the frequency of SCE. Since "in vitro" studies of lymphocytes exposed to transient electric currents (spark discharges) produced similar results the increase in chromosomal damage in substation workers may be associated with exposure to transient electric currents during work.

Genotoxicity evaluation of the tricyclic antidepressants amitriptyline and imipramine using human lymphocyte cultures.

Two tricyclic antidepressants, amitriptyline and imipramine, were evaluated for their in vitro cytogenetic effects in human lymphocyte cultures. Peripheral blood cultures from three normal healthy donors were set up for 72 hr for each of the drugs. The drugs were added at the start (72-hr exposure), 24 hr (48-hr exposure), and 48 hr (24-hr exposure) after initiation of the cultures. The concentrations evaluated at each exposure time were 50, 250, 1,000, and 10,000 ng/ml for amitriptyline and 25, 500, and 5,000 ng/ml for imipramine. The first two concentrations correspond to the plasma levels of the respective drugs after therapeutic doses. All treatments for a donor were given at the same time. Untreated cultures served as controls for the baseline frequency of the parameters assayed. The parameters assayed were chromosome aberrations, mitotic index, and sister chromatid exchanges (SCEs). Amitriptyline was found to be nongenotoxic at plasma levels by all the parameters assayed. However, frequencies of chromosome aberrations and SCEs were significantly increased at concentrations 4 and 40 times the plasma level (1,000 and 10,000 ng/ml) although the actual increases was small. The mitotic index was not affected at any concentration. Through imipramine showed a significant increase in chromosome damage at the upper plasma level and at concentrations higher than that, SCE frequency was significantly increased only at concentration higher than the plasma level (5,000 ng/ml), the actual increase being small for both these parameters. The mitotic index was not affected at any concentration. These results suggest that amitriptyline may be a slightly safer drug than imipramine from a genetic point of view.

Increased chromosome damage in pediatric heart catheterization patients after diagnostic fluoroscopy and cineangiography

Chromosome damage (CD) and sister chromatid exchange (SCE) levels were studied in lymphocytes from 30 pediatric heart catheterization patients receiving radiation during diagnostic fluoroscopy and cineangiography procedures. Forty-eight-hour CD and 72-hr SCE cultures were prepared from sequential samples taken from each patient: samples 1-3 via the catheter the same day (1) before exposure, (2) after fluoroscopy, and (3) after cineangiography; and sample 4 by venipuncture the next morning. Significant increases in CD (dicentrics, rings, and fragments), but not SCE, were observed. From a mean base level of 0.4% cells with CD, the CD levels increased 2-3-fold in samples 3 and 4 (p = .001). Rings only occurred in samples 3 and 4. While increased CD levels also correlated with increasing age, body surface area, and weight, partial correlations controlling for these factors clearly indicate that the CD effects are principally attributable to the radiological procedures (p = .001). Increased CD levels correlated with both the roentgen dose of cineangiography exposure (p = .002) and the volume of contrast medium (p = .000); however, partial correlations, controlling for either factor, indicate that the contrast medium was the principal factor (p = .006).

Low doses of pulsed ultrasound and chromosomal abnormalities in male mouse germ cells

Male mice were exposed to pulsed ultrasound (intensity less than 1 mW, frequency 3.5 MHz) for 30 min or to sham treatment. After 30 h, 11, 12 or 13 days, the testes were cytologically and histologically examined (using squash preparations, air-drying and sections). The resulting damage was studied at diakinesis-metaphase I and II, spermatogonial metaphase and anaphase. The investigation by air-drying did not show any significant increase in chromosome damage, 30 h, 11, 12 and 13 days after treatment (spermatogonial and spermatocytic metaphases). There was, however, a significant increase of the frequency of aneuploid cells detected at metaphase II. Investigations by squash techniques or sections did not reveal adverse effects on the spindles at spermatogonial and spermatocytic anaphases. We suggest that the reduction of fertility previously observed in our clinic could be explained by an increase of aneuploidy if germ cells are exposed to ultrasound during diakinesis of the first meiotic division.

The unique sensitivity of Walker rat tumour cells to difunctional agents is associated with a failure to recover from inhibiton of DNA synthesis and increased chromosome damage

The rate and modle of DNA synthesis was examined by thymidine uptake and by flow cytometry in Walker tumour cells highly sensitive to difunctional agents (WS), and in a derived subline of resistant cells (WR) (Rawlings and Roberts, 1986), following their treatment with sulphur mustard. Both cell lines exhibited the same dose-dependent and progressive depression in rate of DNA synthesis for up h after treatment. Thereafter the depression in rate of synthesis was partially reserved in the WR cells but DNA synthesis continued to decrease in the WS cells resulting in their slower transit through the S phase and a persistent block in the G 2/M phase of the cell cycle. Sensitive cells which finally escaped the block in G 2 carried more chromosome aberrations than the corresponding resistant cells. Neither cell line was defective in daughter strand-gap repair. In the sensitivity to difunctional but not to monofunctional compounds, their failure to recover from the early depression of DNA synthesis, their apparent lack of a defect in excision repair and their sensitivity to chromosome aberration induction, the Walker cell phenmotype closely resembles that of the human Fanconi's anaemia cell.

The effect of thymidine on the induction of micronuclei by alkylating agents in V79 Chinese hamster cells

Incubation in thymidine-containing medium resulted in increased lethality and micronucleus frequency in V79 cells treated with ethyl nitrosourea (ENU), methyl nitrosourea (MNU) and ethyl methanesulphonate (EMS) but not with methyl methanesulfonate (MMS). Thymidine had no effect in ENU treated HeLa cells. In V79 cells, the presence of thymidine during post-treatment DNA replication was necessary for the effect. It is suggested that the increase in chromosome damage was the result of an increased O 6-alkylguanine-thymine mispairing in cells which are defective in the repair of O 6-alkylguanine. Treatment of V79 cells with O 6-ethylguanine resulted in increased production of both micronuclei and polyploid cells. These effects might be explained by spindle dysfunction caused by the alkylated guanine.

Mutagenic efficiency of organophosphorus insecticides used in combined treatments.

Male mice (Q strain) received two consecutive injections of organophosphorus insecticides: a phosphonate (trichlorfon) was combined to a thiophosphate (methylparathion) or a dithiophosphate (malathion or methylazinphos) in order to evaluate the interactions at the genetic and cytogenetic levels. No increase in chromosome damage was observed in bone marrow cells, spermatogonia, and primary spermatocytes. In a dominant lethal mutation assay, the frequency of postimplantation lethality was not significantly increased over the control level. The percentage of preimplantation losses was enhanced, probably due to a toxic effect on male germ cells.

Parallel increases in sister-chromatid exchanges at base level and with UV treatment in human opiate users

The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G 1 and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corroborate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism.

A comparison of the cytogenetic response to asbestos and glass fibre in Chinese hamster and human cell lines: Demonstration of growth inhibition in primary human fibroblasts

Asbestos and fine glass fibre, which induce high levels of chromosome aberrations and polyploidy in Chinese hamster permanent cell lines, were found to cause no increase in chromosome damage or polyploidy in primary human fibroblasts or in human lymphoblastoid lines. In common with permanent cell lines of hamster or human origin, treatment of primary human fibroblasts with higher doses of asbestos or fine glass resulted in almost total growth inhibition, showing that the primary cells are not unaffected by these agents. The reason for lack of evident cytogenetic damage in primary cells may lie in the greater spontaneous karyotype instability of transformed (permanent) cell lines or may be connected with the less efficient DNA repair capacity of Chinese hamster ovary cells.

CHROMOSOME STUDIES OF PATIENTS ON LONG‐TERM LITHIUM THERAPY FOR PSYCHIATRIC DISORDERS

Chromosome studies, including sister chromatid exchange techniques, were performed on blood samples from 23 patients receiving long-term, continuous lithium therapy for psychiatric disorders. Nineteen healthy, age-matched individuals were used as controls. No increase in chromosome damage was detected, when samples from the lithium group were compared with the control group samples.

SPERM ABNORMALITIES AND CIGARETTE SMOKING

Sperm samples from a carefully matched group of 43 cigarette smokers and 43 non-smokers attending an infertility clinic were examined for morphological abnormality. The smokers were found to have a significantly greater percentage of abnormal forms. In the light of other work showing increased chromosome damage in blood lymphocytes of cigarette smokers and of the known propensity for mutagens to induce sperm abnormalities in animals, it is suggested that the sperm abnormalities in cigarette smokers may reflect genetic damage to these cells as a consequence of exposure to smoke products.

Absence of a clastogenic factor in ataxia telangiectasia lymphoblastoid cells

Based on the observation of a diffusable “clastogenic factor” in the plasma of ataxia telangiectasia (AT) patients and the medium used to culture their skin fibroblasts, studies were performed to discern its possible presence in AT long-term lymphoblastoid cell lines. Cocultivation of normal and AT lymphoblasts showed no increase in chromosome damage in the normal cells. Additionally, tissue culture medium, used for the propogation of the AT lymphoblasts, demonstrated no damaging effect on the chromosomes of normal phytohemagglutinin-stimulated lymphocytes. Therefore, contrary to the findings in other cell types (T lymphocytes and skin fibroblasts), the AT B cell apparently does not produce this clastogenic factor.

A diffusable clastogenic factor in ataxia telangiectasia.

Cocultivation of plasma and lymphocytes from ataxia telangiectasia (AT) patients with those of normal individuals resulted in a significant increase in chromosomal damage in the normal cells. Tissue culture medium used to cultivate AT skin fibroblasts also significantly increased chromosome breakage in PHA-stimulated normal lymphocytes. This clastogenic effect was maximal when the "conditioned medium" was 8-9 days old. A similar effect was not observed with medium derived from normal skin fibroblasts. These observations suggest the presence of a clastogenic factor in the plasma of AT patients which may also be produced by AT skin fibroblasts in culture.

Radiation-induced chromosome aberrations in nuclear-dockyard workers.

The incidence of chromosome aberrations in peripheral blood lymphocytes of 197 dockyard workers has been followed over a 10-yr period. These workers were exposed to mixed neutron-gamma radiation during the refuelling of nuclear reactors, but most exposures were below the internationally accepted maximum permissible level of 5 rem per yr. There was a significant increase in chromosome damage with increasing exposure; aberration frequency was a linear function of dose and was unfluenced by age and time of blood sampling after exposure.

Studies on the clastogenic effects of biologic stains and dyes

We have surveyed the clastogenic potential of 12 different groups of stains and dyes totalling 48 compounds. We observed that 18 compounds induced significant increase in chromosome damage. Most of them were also found to be mutagenic, carcinogenic, or toxic in other reported studies. However, no significant studies were reported on six of them. It is concluded that these agents are potentially harzardous and should be studied further in detail.

EFFECT OF RADIATION AND CONTRAST MEDIA ON CHROMOSOMES

In recent years, the complexity of diagnostic cardiac catheterization and angiocardiography had increased greatly resulting in the performance of more angiocardiograms per study and the lengthening of exposure time. We have measured the chromosome aberrations in blood samples obtained from one child immediately before and for 3 years after 70 min. of radiation during cardiac catheterization and angiocardiography and the micronuclei in blood samples obtained immediately before and after similar studies from 5 children. An increase in chromosome damage was observed in all patients. The absorbed radiation dose estimated from the chromosome damage, on the order of 50 rads, was an order of magnitude larger than the estimate based on measurements of x-ray exposure rates. Subsequently in vitro studies were performed in peripheral blood cells to determine the separate effects of contrast agents and/or radiation on chromosome damage and production of micronuclei. The data clearly indicate that exposure of the cells to 5% solutions of Renografin or Hypaque alone for 30 minutes increases the yield of chromosome breaks and micronuclei to levels comparable to those found in our patients after angiocardiography. The ability of contrast media to break chromosomes in the absence of radiation indicates a hazard in their use to tissues outside the x-ray beams and for times much longer than the x-ray exposure.

Chromosome studies in users of spray adhesives.

Chromosome studies were performed on blood samples from eight male subjects stated to have had considerable exposure to spray adhesives in the course of their employment. Eleven healthy males were used as controls. No increase in chromosome damage was found in the exposed subjects compared with the control group.

Comparison of Chromosome Breakages in Lymphocytes and Fibroblasts from Control Women and Women Taking Oral Contraceptives

To determine whether exposure to synthetic hormones resulted in increased chromosome damage in cells other than lymphocytes, we evaluated series of lymphocyte and fibroblast cultures from five control women and five women taking oral contraceptives (OC). The results of this study showed: (1) no difference in chromosome breakages between lymphocytes and fibroblasts; (2) no differences in breakages in replicate fibroblast cultures exposed to fetal calf serum, autologous serum, homologous serum, or homologous serum from OC users; (3) no difference in breakage between lymphocyte and fibroblast cultures from OC users, compared with lymphocyte and fibroblast cultures from control women; and (4) no increase in the frequency of cytogenetically aberrant stem-lines in fibroblast cultures from women taking OC. These findings suggest that synthetic hormones do not cause increased chromosome breakages in fibroblasts from women taking OC.

Response to X-rays of dormant and non-dormant seeds of Triticum durum desf

The X-ray sensitivity of dry seeds of durum wheat at different levels of dormancy was examined. Two doses of X-ray exposures (1000 and 5000 R) were utilized and analysis was carried out on cells from root to tip meristems of seeds allowed to germinate on moistened filter paper for different times. The results showed that the 1000 R dose did not increase the spontaneous chromosome damage in deep dormant seeds, while inducing a 100% increase in chromosome damage in lightly dormant and in non-dormant seeds. The deep dormant seeds irradiated with 5000 R showed a chromosome damage lower than that of both lightly dormant and non-dormant seeds. The chromosome damage was of chromatid type (B′) at 1000 R, irrespective of the physiological condition of the seeds. On the contrary, the lightly dormant or non-dormant seeds irradiated with 5000 R showed both chromatid and chromosome (B″) damage; the deep dormant seeds exhibited B′ damage only. The lack of B″ damage in root meristems from deep dormant seeds is likely to be due to ( i) the physiological state of seeds which causes a slow germination and a possible delay of mitosis initiation at germination, ( ii) a more efficient repair process or a greater radiation resistance bound to the metabolic condition of the deep dormant seeds.