Nitroso-aldicarb induces sister-chromatid exchanges in human lymphocytes in vitro

Nitroso-aldicarb was tested for its ability to induce sister-chromatid exchanges (SCE) and cell-cycle delay in human peripheral blood lymphocytes in vitro. This derivative of aldicarb induced a dose-dependent increase in SCE values per cell. In addition, a slight decrease in the successive mitotic progression of cells in culture was observed.     

Urethane and hydroxyurethane induce sister-chromatid exchanges in cultured human lymphocytes.

Both urethane and hydroxyurethane induced sister-chromatid exchanges (SCE) in cultured human lymphocytes. Aroclor-induced rat-liver microsome fraction deactivated rather than activated these two agents in the lymphocyte system.     

Genotoxic effects of thiram evaluated by sister-chromatid exchanges in human lymphocytes

The purpose of this investigation was to study the genotoxic potential of thiram (CAS No. 137-26-8) using an in vitro sister-chromatid exchange (SCE) assay with human lymphocytes. The results indicate that thiram and its metabolites increase the SCE frequencies 2-fold over those observed in the negative controls. The standard inducers cyclophosphamide and ethyl methanesulfonate increased SCE frequencies 10- and 4-fold, respectively, over untreated levels.     

The effects of beta-radiation on sister-chromatid exchanges in cultured human lymphocytes.

The incidence of Sister-Chromatid Exchanges (SCEs) due to beta-radiation was investigated in cultured human lymphocytes using the BrdU/Giemsa technique. Cultures treated continuously with 0.001 and 0.01 microCi of [3H]uridine showed no increase in either chromosome abnormalities or SCEs. Continuous treatment with 0.1 microCi resulted in a significant increase in chromosome aberrations but no increase in SCEs, while treatment with 0.2 microCi gave both an increase in chromosome aberrations and SCEs. Cultures given a 4-h pulse with 1.0 microCi showed a significant increase in both SCEs and chromosome aberrations. The results indicate that low levels of beta-radiation do not cause an increase in SCEs in human lymphocytes, and, that a number, if not all the exchanges observed at low levels of beta-radiation with autoradiography, may be spontaneous events.     

1,3-Butadiene and its epoxides induce sister-chromatid exchanges in human lymphocytes in vitro

Sister-chromatid exchanges (SCEs) were induced in human lymphocytes by 1,3-butadiene and its epoxides 3,4-epoxy-1-butene and 1,2:3,4-diepoxybutane. After a pulse treatment of 2 h, 1,3-butadiene produced a weak but reproducible increase in SCEs both with and without S9 mix. The response was similar in cultures of whole blood and of isolated lymphocytes. The 2 epoxide metabolites of butadiene, studied in whole-blood lymphocyte cultures without exogenous metabolic activation, were highly active SCE inducers. The lowest effective concentrations of butadiene, monoepoxybutene, and diepoxybutane were 2000 microM, 25 microM and 0.5 microM, respectively. A slight but dose-dependent increase in SCEs was also observed without an exogenous metabolic system after a 48-h treatment with 1,3-butadiene. Already the lowest concentration tested (500 microM) was effective. Again, the response was similar in cultures of whole blood and isolated lymphocytes, suggesting that the lymphocytes are capable of metabolically activating 1,3-butadiene.     

Induction of sister-chromatid exchanges in human lymphocytes by microsomal activation of benzene metabolites

Metabolic activation of the benzene metabolites, catechol, hydroquinone, and phenol, by rat-liver microsomes and an NADPH-generating system (S9 mix) caused an increased induction of sister-chromatid exchanges (SCEs) in cultured human lymphocytes. There were different optimal concentrations of S9 mix for converting each benzene metabolite into further reactive forms that could induce SCE-forming lesions. The data indicate that catechol and hydroquinone can be optimally metabolized to produce reactive species, presumably benzo(semi)quinones, under conditions of lower metabolic activity than those necessary for phenol and benzene.     

Detection of sister-chromatid exchanges in human peripheral lymphocytes induced by ethylene dibromide vapor

A method using sister-chromatid exchanges (SCEs) for genotoxic testing of gaseous compounds is described. Human peripheral lymphocyte cultures previously stimulated with phytohemagglutinin were placed in sterile dialysis tubing and then put in an enclosed flask containing additional culture media. Air, with or without ethylene dibromide (EDB), was bubbled through the flask for up to 8 h. The cultures were harvested 75 h after culture initiation, and second-division cells were scored for induction of SCEs according to established procedures. The SCE frequency was approximately doubled in cultures treated with EDB. A similar experiment with air alone resulted in only slight increases in SCEs. The results indicate that this system is potentially useful for detecting genotoxicity of gases and vapors and may be useful for the detection of genotoxic agents in occupational settings.     

Induction of sister-chromatid exchanges in cultured human lymphocytes by Aldicarb, a carbamate pesticide

The aim of this work was to investigate the effects of Aldicarb on human lymphocytes in vitro in the presence of an exogenous metabolic activation system. This was done by means of an analysis of SCE and mitotic delay. CP was used to compare the chromosomal effects of Aldicarb with a known genotoxic agent. Our experiments showed that Aldicarb as well as CP induced a significant increase of SCE values in the absence of S9 mix. In vitro metabolic activation of both chemicals increased the SCE values. The addition of a metabolic system slightly decreased the successive mitotic progression of cells in culture.     

Hypotonic treatment leads to chromosomal aberrations but not to sister-chromatid exchanges in human lymphocytes

Human peripheral lymphocytes were isolated from whole blood and exposed to culture medium of reduced osmolality. This hypotonic treatment led to a significant increase in the frequencies of chromosomal aberrations when the osmolality was reduced to 60 mOsm/kg H2O and below. Maximum damage occurred when the hypotonic treatment was done 27 or 30 h after starting the cultures. We also looked for the induction of sister-chromatid exchanges (SCE) by hypotonic culture conditions, but the SCE frequencies were not influenced.     

Modulation by novobiocin of sister-chromatid exchanges induced by tumor necrosis factor in human lymphocytes.

The effect of the antibiotic novobiocin on human recombinant tumor necrosis factor (TNF)-induced sister-chromatid exchanges (SCEs) were examined in human peripheral blood lymphocytes. TNF, when introduced in a dose range of 10-1000 U/ml at the initiation of culture, was found to cause a significant increase in SCE frequency. The simultaneous addition of TNF and novobiocin (25 micrograms/ml) in the assay resulted in no increase of SCE frequency. Delayed (for 24 h) addition of novobiocin suppressed the induction of SCEs by 50, 100 and 500 U/ml but not by 1000 U/ml of TNF.     

Chromosomal aberrations and sister-chromatid exchanges in lymphocytes from coke oven workers

To test whether coke oven workers, an occupational group known to be at increased cancer risk, manifest increased peripheral blood chromosomal aberration frequencies, we obtained samples from a group of 30 steelworker volunteers, who had worked several years at coke oven jobs. Exposure estimates were made using measurements of work place atmospheric coal tar pitch volatiles and work histories. No statistically significant positive regression of chromosomal aberrations on exposure estimates was found. The data from the coke oven workers were also compared with the obtained concurrently and employing precisely the same laboratory protocol from a group of male Brookhaven National Laboratory employees. The coke oven workers as a group were found to have statistically significantly elevated frequencies of chromatid aberrations and of sister-chromatid exchanges.     

Chloramine-induced sister-chromatid exchanges

Nitrogen-chlorine (N-Cl) derivatives are a class of long-lived oxidants produced by stimulated phagocytes which may be important mediators of the inflammatory response. Because other phagocyte-generated oxidants cause genetic damage in cultured mammalian cells, we studied the ability of the synthetic N-Cl compound, chloramine T (Cl-T), to produce sister-chromatid exchanges (SCEs) in cultured Chinese hamster ovary (CHO) cells. CHO cells were incubated for 30 h with Cl-T (10(-8) M-10(-5) M) and genetic damage was analyzed utilizing the SCE assay. A significant (p less than 0.0005) dose-dependent increase in SCEs was observed. This effect was diminished when cells were treated concomitantly with methionine (10(-5) M), a thioether which reduces N-Cl back to the parent amine. Extracellularly-generated oxidants must traverse long distances before interacting with nuclear target molecules. Therefore, long-lived N-Cl derivatives may represent an important class of oxidants which mediate the process of carcinogenesis associated with chronic inflammatory states in vivo.     

Increased frequency of acetaldehyde-induced sister-chromatid exchanges in human lymphocytes treated with an aldehyde dehydrogenase inhibitor

Acetaldehyde, the first metabolite of ethanol oxidation, in concentrations ranging from 100 microM to 400 microM caused a dose-dependent linear increase in the frequency of sister-chromatid exchanges (SCE) in cultured human peripheral lymphocytes. The SCE frequency was on an average 2-fold higher when the cells were exposed to the acetaldehyde after 24 h incubation instead of at the time of mitogen stimulation (0 h). When acetaldehyde was added together with the potent aldehyde dehydrogenase inhibitor 1-aminocyclopropanol (0.1 mM), the SCE response was significantly (p less than 0.05) increased. The present results indicate that acetaldehyde is metabolized within human lymphocytes, and, moreover, that alcohol consumption during treatment with drugs that inactivate aldehyde dehydrogenase may cause a further increased incidence of acetaldehyde-induced SCE and concomitant lesions.     

Analysis of chromosome aberrations and sister-chromatid exchanges in human lymphocytes exposed in vitro to Hydergine.

Hydergine (dihydroergotoxine mesylate, Sandoz) was examined for its capability to induce chromosome damage and sister-chromatid exchanges (SCEs) in human lymphocyte in vitro. For the chromosome-aberration study, cultures set up from 6 individuals were divided into 5 groups: negative control, positive control (caffeine, 0.5 mg/ml), and Hydergine (0.1, 0.25 and 0.5 micrograms/ml). For the SCE examination, which used 8 individuals, 4 cultures were made per person in the following way: negative control, positive control (mitomycin C, 0.1 microgram/ml), and Hydergine (0.1 and 0.5 micrograms/ml). Lymphocytes were cultivated for 72 h, being exposed to the respective treatments during the final 24 h. The results showed that Hydergine induced no chromosome damage in human lymphocytes in vitro.