Chromosome Aberrations In Peripheral Lymphocytes Research Articles

Time-effect relationship of chromosome aberrations in peripheral lymphocytes after radiation therapy for seminoma.

The time-effect relationship of dicentrics and cells containing unstable chromosome abnormalities (Cu cells) was studied in peripheral lymphocytes of 40 blood samples from 23 patients suffering from seminoma during a time period of 0-1720 days after radiation therapy. Nine patients were studied before treatment. Since the half-time for the disappearance of damaged cells from circulating blood is an increasing function of post-exposure time it can only be expressed as a differential value. The present model discriminates between the mean lifetime m for lymphocytes and a parameter q which is the differential half-time for the decline of damaged cells immediately after exposure (t = 0). If the time t is short compared with m the decline is asymptotically time-hyperbolic rather than exponential and can be described by q only. According to recalculations of previous data, comprising 30 years post exposure, m approximates 10 years. Differential half-times can be derived for any time post treatment within the analysed time period for the decline of the incidence of dicentrics. For example at the end of therapy (t = 0) the differential half-time was calculated to be 0.4 years and at 1720 days post exposure 3.6 years resulted. The corresponding values for the percentage of Cu cells cannot be derived for t = 0; at 1720 days 3.9 years resulted.

SCE and structural chromosomal aberrations in peripheral lymphocytes, urinary mutagenicity and PAH metabolite excretion in psoriatic patients treated with coal tar

SCE and structural chromosomal aberrations in peripheral lymphocytes, urinary mutagenicity and PAH metabolite excretion in psoriatic patients treated with coal tar

Effects of phenoxyacetic acids on the induction of chromosome aberrations in vitro and in vivo.

The effects of phenoxyacetic acid herbicides were investigated on the induction of chromosome aberrations in human peripheral lymphocyte cultures in vitro and in lymphocytes of exposed workers in vivo. Pure 2,4-dichlorophenoxyacetic acid (2,4-D; 0.125, 0.150, 0.200 and 0.350 mM) did not increase the number of aberrations, whereas the commercial 2,4-D formulation (0.125, 0.250, 0.500, 1.000 and 1.250 mM, with respect to phenoxyacetic acid concentration) significantly increased the number of chromosome aberrations in vitro (without exogenous metabolic activation). The phenoxy acid levels in the breathing zone of the workers varied between 0.3 and 0.4 mg/m3, and the concentrations of phenoxyacetic acids in the urine of the workers after exposure varied from 0.000 to 0.055 mmol/l. There were no increases in chromosome aberrations in peripheral lymphocytes of the exposed subjects.

In vitro induction of sister chromatid exchanges and chromosomal aberrations in peripheral lymphocytes of the oyster toadfish and American eel.

A series of experiments was conducted to characterize the proliferation of oyster toadfish lymphocytes in medium containing 5-bromodeoxyuridine (BrdUrd) and to determine the effectiveness of cytogenetic endpoints for assessing the genotoxic effects of in vitro exposure of toadfish and eel lymphocytes to known mammalian clastogens. Although the rate of proliferation of toadfish lymphocytes was low compared to that of mammalian lymphocytes, the effects of increasing BrdUrd concentrations were similar, in that proliferation exhibited a concentration-dependent inhibition for concentrations above 10 microM BrdUrd, and sister chromatid exchange (SCE) frequencies exhibited a concentration-dependent increase for concentrations above 100 microM BrdUrd. Mitomycin C (MMC) and ethylene dibromide (EDB) induced concentration-dependent increases in chromatid-type exchange and SCE frequencies with least effective concentrations (control SCE frequency divided by the slope of the least-squares line) for SCE induction by MMC (6.8 X 10(-9) M) and EDB (2.6 X 10(-4) M) that were comparable to or slightly lower than those that have been obtained with mammalian in vitro systems. In vitro exposure of toadfish lymphocytes to dimethoate (DIM) induced a concentration-dependent increase in SCE frequency with a least effective concentration of 2.8 X 10(-3) M that was much higher than that observed with mammalian in vitro systems. In vitro exposure of American eel lymphocytes to MMC also induced a concentration-dependent increase in the frequency of chromosomal aberrations and SCEs with a least effective concentration for SCE induction of 2.0 X 10(-9) M. These results indicate that cytogenetic endpoints can be effectively scored with cultured lymphocytes from these and perhaps other fish species with comparable karyotypes that contain an average of at least 0.07 pg DNA/chromosome.

Chromosome aberrations in peripheral lymphocytes of male homosexuals

Karyotypes of peripheral lymphocytes of 19 male homosexuals showed increased hypodiploidy. Chromosomes #19 and #20 were most frequently lost. Also, structural chromosome aberrations frequently occurred consisting chiefly of translocations and simple chromosome breaks. Terminal deletions, inversions, and isochromosomes occurred less commonly. In three of the cases, 100% of the cells were involved in a pericentric inversion of a chromosome #9. Chromosomes #3 in p21.1 and 1 in p32.3 were repeatedly affected. Structural aberrations were seen less frequently in men with acquired immunodeficiency syndrome(AIDS) and AIDS-related complex than in asymptomatic homosexuals. The hypodiploidy with preferential loss of chromosomes was constantly present. The marker chromosomes and simple breaks at repeated sites are another manifestation of damage to the immune system in these male homosexuals from Greenwich Village in New York City. The chromosomal damage was potentially the result of exposure to amyl and butyl nitrites, viral infections, or immunologic reactions to sperm, which crossreact with lymphocytes.

Sister-chromatid exchanges and chromosome aberrations in lymphocytes from monkeys exposed to ethylene oxide and propylene oxide by inhalation

The ability of long-term exposures to inhaled ethylene oxide (EO) and propylene oxide (PO) to induce sister-chromatid exchanges (SCEs) and chromosome aberrations in peripheral lymphocytes of monkeys was investigated. Five groups of adult male cynomolgus monkeys were exposed at 0 (shared control), 50, or 100 ppm EO, and at 100 or 300 ppm PO (7 hr/day, 5 days/week) for 2 years. EO exposures at 50 and 100 ppm resulted in statistically significant increases in sister-chromatid exchange rates and in the incidence of chromosome aberrations in monkey lymphocytes. Both EO-exposed groups had increased numbers of SCEs/metaphase compared to controls, with the SCEs/metaphase of the EO 100 ppm group also significantly elevated versus the EO 50 ppm group. Variability of SCEs/metaphase within each monkey increased even more than the increase in total SCEs/metaphase group with increasing EO exposure. Chromatid-type aberrations were also significantly increased for both EO 50 and EO 100 ppm groups compared to controls. Statistically significant increases in the number of chromosome-type aberrations (excluding gaps) were found only in the EO 100 ppm group. Combined chromatid- and chromosome-type aberrations were increased in both EO 50 and EO 100 ppm groups. No group differences in the number of gaps were found. In lymphocytes from monkeys exposed at 100 and 300 ppm PO, there were no group differences compared to controls for any variable-chromatid or chromosome-type aberrations, gaps, or SCEs/metaphase. These results indicate that EO is a more potent clastogen than PO and demonstrate, for the first time, statistically significant effects of EO on both SCEs and chromosome aberrations in lymphocytes of nonhuman primates.

Increased incidence of chromosomal aberrations in peripheral lymphocytes of retired nickel workers.

Chromosomal aberrations and sister chromatid exchanges were analysed in the peripheral lymphocytes of nine retired nickel refinery workers 4-15 years after the retirement and compared with 11 matched non-nickel exposed controls. None of the controls had previous occupations with known relation to induction of chromosomal aberrations nor sister chromatid exchanges. The groups were equal as to socioeconomic status and environmental factors other than the occupational ones, which could influence the chromosome parameters, were to the largest possible extent excluded. The nickel workers' previous occupational employment involved exposure to inhalation of furnace dust of Ni3S2 and NiO or aerosols of NiCl2 and NiSO4. The concentration of nickel in the working atmospheres has been higher than 1.0 mg/m3 air and the exposure time more than 25 years. The retired nickel workers showed an increased incidence of breaks (p less than 0.001) and gaps (p less than 0.05) but no difference in the incidence of sister chromatid exchanges when compared with the controls.

Effect of occupational exposure to epichlorohydrin on the frequency of chromosome aberrations in peripheral lymphocytes

The relationship between the level of occupational exposure to epichlorohydrin (ECHH) and the clastogenic effect was studied on a group of 33 workers. The effect of ECHH was assessed by differences in the frequency of chromosome aberrations in peripheral blood lymphocytes in ECHH-exposed and control groups. In the group exposed to the average ECHH concentration, 0.384 mg ·m −3, during the last 6 months, the cytogenetic analysis revealed 2.00 ± 0.23% AC (aberrant cells) (0.0203 B/C, breaks per cell) as compared with 1.68±0.23% AC (0.0172 B/C) in the matching controls. These results indicate that an average concentration lower than 0.40 mg·m −3 ECHH in the working atmosphere has no significant clastogenic effect on human peripheral lymphocytes.

Sister chromatid exchanges and structural chromosome aberrations in lymphocytes in operating room personnel.

Information on possible chromosomal damage in humans after long-term exposure to trace concentrations of waste anaesthetic gases is scarce. We examined peripheral lymphocytes in operating room personnel for both chromosome aberrations and sister chromatid exchanges (SCE). Following a standardized procedure of cultivation and staining, 30 cells from each person were scored for SCE and 100 cells from each person were examined for chromosome aberrations. A total of 45 persons were examined, representing anaesthetists (n = 15), operating room nurses assisting the surgeon (n = 10), nurses circulating in the operating room (n = 8) and healthy, unexposed controls (n = 12). The median duration of working in the operating room was 102 months, 66 months and 66 months, respectively. Time-weighted concentration levels of 2.5-4.3 p.p.m. of halothane and 25-400 p.p.m. of nitrous oxide were measured in the breathing zones of the anaesthetists during mask anaesthesia. Examination of SCE and chromosome aberrations yielded corresponding qualitative results. With both tests, no statistically significant difference was observed between the four groups of persons. It was concluded that by examination of both SCE and chromosome aberrations in peripheral lymphocytes in operating room personnel, no indication was found of a mutagenic effect of long-term exposure to trace concentrations of waste anaesthetic gases.

Effect of ascorbic acid prophylaxis on the frequency of chromosome aberrations in the peripheral lymphocytes of coal-tar workers

The possible anti-mutagenic potential of prophylactically administered ascorbic acid (AA) preparations was studied in a group of 35 coal-tar workers occupationally exposed to PAH and benzene. The effectiveness of AA prophylaxis was assessed by differences in the frequency of chromosome aberrations in peripheral blood lymphocytes of the exposed workers examined before and after a 3-month treatment with AA at the daily doses of 1.0 g for 5 days a week. In the exposed group the cytogenetic analysis of peripheral blood lymphocytes revealed a significant drop in the frequency of aberrant cells (AB.C.) from the initial 5.07% AB.C. (0.0657 B/C, breaks per cell) to 1.77% AB.C. (0.0197 B/C). In a group of matching controls the frequency of AB.C. was 1.50% (0.0170 B/C) and 1.45% (0.0180 B/C), respectively. The study showed that the risk of genetic injury assessed by the frequency of chromosome aberrations in peripheral blood lymphocytes was substantially reduced after AA prophylaxis.

Chromosomal aberrations in peripheral lymphocytes of patients examined by computer tomography with or without contrast medium

Chromosomal aberrations in peripheral lymphocytes of patients examined by computer tomography with or without contrast medium

Effect of photochemical smog on the peripheral lymphocytes of nonsmoking college students

The primary objective of this study was to determine whether the incidence of chromosome aberrations in peripheral lymphocytes of young adults emigrating from and immigrating to an area with perpetually high levels of photochemical air pollutants versus an area of low levels differed significantly from students indigenous to the respective areas. Three hundred and ninety-eight male and female first-year students at the La Sierra campus of Loma Linda University (high smog) and Pacific Union College (low smog) were preenrolled after completing a lifestyle questionnaire or responding to a similar telephone-administered questionnaire. They were assigned to groups according to their previous lifetime exposure to air pollution and the college in which they were matriculating. Blood samples and updated health histories were obtained from the students during September and November 1976. One hundred cells from each student were analyzed for chromosome and chromatid abberations. No statistically significant differences in the aberration rates for the types of chromosome abnormalities studied were observed between the four exposure groups of students at each of the sampling periods or among the same students over the duration of the study. An exception of statistical significance was the elevated rate of stable changes at the initial blood sampling period for males in the low-to-high exposure group who had arrived on campus within 3 days of the blood sampling.

In vivo and in vitro ethylene oxide exposure of human lymphocytes assessed by chemical stimulation of unscheduled DNA synthesis

Factory workers exposed to ethylene oxide (EO), 0.5–1.0 ppm in factory air, together with matched controls from the same factory, were examined for evidence of toxic exposure by measurement of unscheduled DNA synthesis (UDS) induced by N-acetoxy-2-acetylaminofluorene (NA-AAF) and of chromosome aberrations in peripheral lymphocytes. The total chromatid gaps plus breaks were significantly elevated and NA-AAF-induced UDS was significantly reduced in the EO-exposed group as compared with the unexposed control group. The NA-AAF-induced UDS values negatively correlated to the duration (yr) of EO exposure ( r = −0.45, p < 0.02) and the number of chromosome breaks ( r = −0.61, p < 0.05), indicating an inhibition in vivo of DNA-repair capacity by EO. These data were verified in vitro by biochemical and autoradiographic studies of EO-induced UDS in human blood cells. Above 2 mM EO, UDS was inhibited in lymphocytes whether they were cultured for 24 or 122 h after alkylation with EO. Even at the subtoxic EO dose of 0.1 mM, lymphocytes were sensitized to additional exposures of NA-AAF, so that cytotoxicity was increased to 40% compared with 5% for the controls even though UDS was unaffected. It is concluded that EO was toxic to lymphocytes, even when they were sensitized at non-toxic EO doses to the cytotoxic action of other mutagens (e.g. NA-AAF), and the cells that did survive above 2 mM EO were inhibited in their DNA-repair capacity as judged by reduced UDS.

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 vairance, 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.

Induction of chromosomal aberrations in peripheral lymphocytes of human blood in vitro, and of SCEs in bone-marrow cells of mice in vivo by ethanol and its metabolite acetaldehyde

Induction of chromosomal aberrations in peripheral lymphocytes of human blood in vitro, and of SCEs in bone-marrow cells of mice in vivo by ethanol and its metabolite acetaldehyde

Styrene, its metabolism and the evaluation of hazards in industry.

The main products of styrene biotransformation excreted in human urine are mandelic and phenylglyoxylic acids. Phenylethylene oxide seems to be the first metabolite; this compound has been reported to be mutagenic and carcinogenic. The polarographic determination of mandelic acid has been used for about 20 years in Czechoslovakia as an exposure test for persons occupationally exposed to styrene. Only single cases of health damage have been reported to be due to styrene exposure during this time. Recently, however, elevated frequencies of chromosomal aberrations in peripheral lymphocytes have been observed in persons exposed to styrene in Czechoslovakia. The amount of phenylethylene oxide that can be formed in the human body during exposure to 50 ppm of styrene in air during a workshift is about 0.7 g. It would be hardly justifiable now to believe that styrene is not carcinogenic and mutagenic in man. The present Czechoslovakian maximum allowable concentration of styrene (200 mg/m3) should be reduced, and the concentration of 50 mg/m3 may be recommended as reasonable at this time. The corresponding biological limit value of mandelic acid might be 300 mg/l of urine from the last 2 h of the workshift.

Chromosomal aberrations in peripheral lymphocytes of patients with multiple sclerosis (author's transl)

In chromosomes of peripheral lymphocytes of 35 patients with multiple sclerosis treated with azathioprine, antilymphocytic globulin or thoracic-duct drainage structural aberrations (breaks and gaps) were found at a significantly high rate. The aberration rates were increased in another ten untreated patients as well, but less so. Patients previously treated had a high aberration rate, too. The B- and C-chromosomes of patients treated with azathioprine were more frequently involved than those of control subjects. The terminal segment of the long arm of chromosome 1 was mostly affected in these patients, while in all groups there was an increase of aberrations in the centre of the long arm of the C-chromosome. The clinical significance of these chromosomal aberrations is not yet clear.

エリテマトーデスとリンパ球

Three studies were carried out on the lymphocytes of the patients with Lupus Erythematosus in order to: (1) look for chromosomal aberrations in peripheral lymphocytes; (2) examine the function of immunologically competent lymphoid cells (cellular antibody); (3) determine the presence or absence of immunoglobulin production by cultured peripheral lymphocytes. Various chromosomal aberrations were frequently observed in cultured lymphocytes from patients with SLE, but few in DLE. Significantly increased frequency of chromosomal aberrations in SLE, especially G group chromosomal abnormalities including G trisomy, suggests that there is an association between chromosomal abnormalities and autoimmune disease. The examination of delayed hypersensitivity indicated that there was a functional failure of immunologically competent lymphoid cells in SLE. The direct immunofluorescent staining showed that PHA stimulated lymphocytes from patients with SLE contain γ-globulin, IgG and IgM. It seems likely that these cells produce each immunoglobulin.

Chemical Radiation Protection in Man as Revealed by Chromosome Aberrations in Peripheral Lymphocytes

Patients with cervical carcinoma under radiotherapy have been followed during and after radiotherapy for the incidence of chromosome aberrations in peripheral lymphocytes. In patients treated with adrenochrome monoguanylhydrazone methansulfonate (100 mg) before every irradiation the incidence was significantly lower than in those without the treatment. The result indicates chemical protection in man for the first time.