Sister-chromatid exchanges (SCE) induced by p-dichlorobenzene in cultured human lymphocytes

We have investigated the ability of p-dichlorobenzene (p-DCB) to induce sister-chromatid exchanges (SCE) in cultured human lymphocytes. From our results we can conclude that p-DCB was able to induce a cytotoxic effect, measured as a decrease in third and second metaphases, together with an increase of SCEs.     

Sister-chromatid exchanges induced by vinyl esters and respective carboxylic acids in cultured human lymphocytes.

Vinyl acetate--an efficient inducer of sister-chromatid exchanges (SCEs)--is known to be hydrolyzed in mammalian cells into acetic acid and acetaldehyde, the latter being the likely metabolite responsible for the SCE induction. As similar hydrolysis to acetaldehyde and to a carboxylic acid is also expected for other vinyl esters, five such compounds--vinyl formate, vinyl chloroformate, vinyl propionate, vinyl crotonate and vinyl-2-ethylhexanoate--and five carboxylic acids--formic acid, acetic acid, propionic acid, crotonic acid and 2-ethylhexanoic acid--were tested for their ability to induce SCEs in cultured (72 h) human lymphocytes with a 48-h treatment, starting at 24 h after culture initiation. Vinyl formate, vinyl propionate and vinyl crotonate induced a clear dose-dependent increase in the number of SCEs/cell at concentrations of 0.125-0.5 mM and vinyl chloroformate at 0.063-1 mM, i.e., at roughly the same concentration range as vinyl acetate and acetaldehyde. Vinyl-2-ethylhexanoate required slightly higher concentrations (0.25-4 mM) for SCE induction. All of the carboxylic acids tested also elevated SCEs, but only slightly. Formic acid and crotonic acid produced some SCE increase at a concentration of 10 mM, acetic acid at 5 and 10 mM and propionic acid at 2.5 mM. 2-Ethylhexanoic acid induced SCEs at a lower concentration range (0.63-2.5 mM) than the other acids. The positive concentrations of the first three carboxylic acids lowered the pH of the culture medium immediately after the treatment by 0.5-1.0 pH unit (lowest observed pH 6.53). The pH differences from the control cultures became smaller in measurements done 24 h and 48 h after the beginning of treatment. Propionic acid and 2-ethylhexanoic acid affected medium pH only slightly (maximum drop 0.2 pH units) at the concentrations that induced SCEs. The results lend support to the idea that the efficient SCE induction observed with the vinyl esters results from the formation of acetaldehyde, with carboxylic acids--with the possible exception of 2-ethylhexanoic acid--playing no significant role. The slight SCE induction obtained with the carboxylic acids cannot be explained by lowered pH alone.     

Sister-chromatid exchanges induced in swine lymphocytes by chronic oral doses of dimethylbenzanthracene

Sister-chromatid exchanges were scored at 3-week intervals in lymphocytes of female swine ingesting daily doses of 1.25 or 2.50 mg/kg of 7,12-dimethylbenzanthracene (DMBA) for 160 days. Exchanges increased with time for about 120 days then reached a plateau at approximately 2.5 times their pretreatment level. No increase in chromosome aberrations could be identified as resulting from ingestion of the chemical. Week-old progeny of animals that had ingested the chemical throughout pregnancy showed no increase of exchanges in their peripheral lymphocytes.     

Bloom's syndrome. IV. Sister-chromatid exchanges in lymphocytes.

An abnormally great amount of exhange between both sister and nonsister-but-homologous chromatids is a highly characteristic feature of cultured blood lymphocytes from individuals with Bloom's syndrome. However, a population of lymphocytes which exhibit a normal amount of exchange can be detected in the blood of some individuals with this syndrome. This coexistence of cells with a greatly increased number of sister-chromatid exchanges and others with a normal number results in a phenotypic dimorphism, in apparent contradiction to the autosomal recessive mode of inheritance of the syndrome.     

Sister-chromatid exchanges in human lymphocytes exposed in vitro to therapeutic ultrasound

Human lymphocytes were exposed in vitro to therapeutic levels of ultrasound (1 W/cm2, CW, 0.87 MHz, durations of 80 and 160 sec). There were no significant differences in sister-chromatid exchange frequencies between controls and ultrasound-exposed cells. Exposure of lymphocytes to the positive control (mitomycin C) resulted in a significant increase in sister-chromatid exchanges. The data do not verify a report by Stella et al. (Mutation Res., 138 (1984) 75-85) that such exposures result in increased frequencies of SCEs.     

Sister-chromatid exchanges in human lymphocytes treated with 4-chloromethylbiphenyl and benzyl chloride

At non-inhibitory concentrations, 4CMB and BC both induced small, but dose-related increases in SCE. The dose-response curves gave a highly significant correlation for 4CMB (r=0.996, P<0.001) and a significant correlation for BC (r=0.757, P<0.05) which reflects the relative activities of these substances in bacterial mutation tests.     

Sister-chromatid exchanges in lymphocytes from styrene-exposed boat builders

Sister-chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 40 workers in the boat-building trade. Twenty of these workers were exposed to significant amounts of styrene. The mean air concentration of styrene in the breathing zone of the boat builders was 209 mg/m3 in the 7 exposed current smokers and 230 mg/m3 in the 13 exposed non-smokers. Urinary styrene metabolites were also measured and the mean mandelic acid/creatinine ratios in the exposed, smokers was 275 mg/g, and in the exposed, non-smokers 323 mg/g. The SCE frequency in lymphocytes from the styrene-exposed group did not differ from that in the controls, although smoking significantly induced SCE in these workers.     

Sister-chromatid exchanges in lymphocytes from patients with Schistosoma hematobium

Sister-chromatid exchange (SCE) frequencies were studied in peripheral blood lymphocytes from 19 patients (13 males and 6 females) with Schistosoma hematobium, prior to the initiation of chemotherapy. The mean frequency of SCE per metaphase for the patients (both sexes) was 10.4 +/- 4.2 which was significantly higher (P less than 0.01) than the mean SCE (6.4 +/- 1.1) score for 35 healthy controls. A highly significant reduction in lymphocyte division and delay in cell-cycle progression as a result of infection were also noticed. These data indicate that infection with S. hematobium could increase SCEs in the host somatic cells.     

Sister-chromatid exchanges in human lymphocytes exposed during Go to four classes of DNA-damaging chemicals.

Human lymphocytes were treated prior to mitogenic stimulation with varying concentrations of 6 cytostatic drugs representing 4 classes of DNA-damaging chemicals. Afterwards the cells were washed to remove residual chemical and cultured in the presence of bromodeoxyuridine for analysis of sister-chromatid exchanges (SCEs). A dose-related increase in SCEs was observed in cells exposed during Go to the alkylating chemicals mitomycin C, chlorambucil, and thiotepa, while significant increases in SCEs were not noted in cultures exposed to methotrexate, cytarabine, or bleomycin. These findings suggest that not all classes of clatogenic chemicals which induce SCEs in proliferative cells substituted with BUdR are capable of inducing long-lived lesions in the DNA of Go lymphocytes that can lead to SCE formation.     

Sister-chromatid exchanges induced by ultraviolet light in Bloom's syndrome fibroblasts

The relationships between the cytotoxic effect of ultraviolet light and the UV-induced sister-chromatid exchanges (SCEs) were compared among fibroblast cell strains from two unrelated Bloom's syndrome (BS) patients, one xeroderma pigmentosum (XP) patient belonging to complementation group A and two unrelated normal controls. The "net" induced SCEs as a function of UV fluence, obtained by subtracting spontaneous SCEs from observed SCEs, were much higher in both BS cells and XP group A cells than in normal cells. The relative efficiency of induced SCE, defined as the "net" induced SCEs as a function of surviving fraction after UV irradiation, was higher in BS cells than in normal and XP cells, and there was essentially no difference between XP and normal cells. These results imply that in addition to the extremely high frequency of spontaneous SCEs, the increased efficiency in UV induction of SCEs may reflect the intrinsic defect(s) in BS cells.     

Sister-chromatid exchanges in lymphocytes of workers exposed to trichloroethylene

To detect mutagenic effects of trichloroethylene (TCE) on humans, sister-chromatid exchanges (SCEs) were analyzed in lymphocytes of 22 workers occupationally exposed to TCE and 22 matched controls. Although urinalysis in the workers revealed their obvious exposure to TCE, no increase in SCE frequencies was found in lymphocytes of the workers. SCE analysis in lymphocytes could not detect mutagenic effects by occupational exposure to TCE on humans.     

Sister-chromatid exchanges in lymphocytes from infants with Down's syndrome

Sister-chromatid exchange (SCE) frequencies were studied in blood lymphocytes from 12 patients (3 females and 9 males) with Down's syndrome (DS). The mean frequency of SCE per metaphase for the patients (both sexes) was 9.2 +/- 0.8 which was significantly higher (P less than 0.01) than the mean SCE value (5.1 +/- 0.2) scored for 16 healthy infants (8 females and 8 males). A significant increase in the mean frequency of SCE in 12 parents of infants with DS (8.7 +/- 0.9 SCE/cell) was noticeable when compared with 20 parents of normal infants (6.3 +/- 0.1 SCE/cell). Increases in cellular division with reduction in their replication were also observed in patients with DS. Treatment with mitomycin C (0.05 micrograms/ml), hycanthone (0.1 micrograms/ml) and gamma-radiation (0.1 Gy) revealed a significant (P less than 0.01) increase in frequencies of SCE in DS lymphocytes and in those of their parents as compared to controls. These data may reveal a familial hypersensitivity reaction to these agents. The results indicate a genomic instability and deranged DNA-repair mechanisms which are accentuated by exposure to mutagenic agents, the underlying causal factor for which might be genetic.     

Sister-chromatid exchanges in lymphocytes of smokers in an experimental study

The frequency of sister-chromatid exchanges (SCEs) was studied in peripheral blood lymphocytes of 26 young male smokers and 10 non-smokers who had recently entered military service. The levels of SCEs were examined in 4 consecutive blood samples taken after short experimental periods of smoking only low-tar (LT) or medium-tar (MT) cigarettes. The incidence of SCEs was significantly higher in the the group of smokers than in the group of non-smokers. The SCE levels of the smokers were found to be associated with the personal smoking history; the observed increase in the SCE frequency correlated with the years of smoking measured as cumulative pack years. The difference in type of cigarette did not influence the SCE frequencies.     

Sister-chromatid exchanges induced by mitomycin C after exposure of human lymphocytes in G0 to a low dose of X-radiation

Human peripheral blood lymphocytes from 20 donors were exposed in G0 to mitomycin C with and without prior acute irradiation with 0.01 Gy of 250 kVp X-rays. No evidence was found for the radiation having an hormetic effect on the level of sister-chromatid exchanges induced by mitomycin C.     

Sister-chromatid exchanges induced by mitomycin C after acute or chronic exposure of human lymphocytes to a low dose of X-rays

Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays. Acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycin C-induced sister-chromatid exchange aberrations. The effect was small (approximately 10%) with evidence of some variability between donors. By contrast no adaptive response was observed if the cells were treated in G0.     

Sister-chromatid exchanges in cannabis smokers.

The genotoxicity of cannabis smoking was evaluated by means of the sister-chromatid exchange (SCE) test. The SCE test is considered to be a sensitive tool for the discovery of genotoxic agents in the environment. Twenty-two tobacco smokers and 22 persons smoking both tobacco and cannabis were compared. Our findings showed that smoking in itself enhanced the SCE level significantly (18.5%) compared to a group of non-smokers, but adding smoking of cannabis to tobacco smoking did not affect the SCE level further. Based on our observations cannabis smoking could not be considered genotoxic.