Neocarzinostatin induces chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells

Chinese hamster ovary (CHO) cells were treated with neocarzinostatin(NCS) and analyzed for chromosomal aberrations and sister chromatidexchanges (SCE). After treatment the cells were recovered for9, 20, 26 or 30 h. NCS induces chromosomal aberrations and SCE.SCE were much more frequent in cells with chromosome type aberrationsat 20 h recovery time than in those with chromatid type aberrationsat 9 h recovery time. In second post-treatment cells at 26 or30 h recovery time NCS induced chromosomal aberrations but onlyfew SCE.     

Adriamycin-induced sister chromatid exchange and chromosomal aberrations in Down's syndrome lymphocytes.

Blood samples from six Down's syndrome (DS) and six age- and sex-matched controls were cultured for 72 h in the presence of BrdUrd. Lymphocytes were then analysed at their second mitosis for sister chromatid exchange (SCE) and at their first mitosis for chromosome aberrations. Treatment with adriamycin (30 and 60 ng) showed a significant increase in frequency of SCE and chromosome aberrations in DS lymphocytes compared to normal lymphocytes at initiation of culture. Cells treated with adriamycin (ADR) for the last 24 h also showed a significant increase in SCE in DS lymphocytes compared to normal lymphocytes. A significant increase in chromatid-type aberrations was also recorded in DS lymphocytes after both treatments cultured for the last 24 h.     

Relationship between carcinogenicity in rodents and the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells

Two independent analyses were carried out to compare the induction of sister chromatid exchanges and of chromosomal aberrations as predictors of carcinogenicity. Using both a classical and a Bayesian approach, as well as by analysis of the structural fragments generated by CASE, an artificial intelligence system, it is included that individually neither of these tests is a satisfactory predictor of carcinogenicity. However, because the analysis revealed that each of the cytogenetic assays responds to a different set of structural features associated with carcinogenicity, it can be concluded that the assays can be included in a battery of tests to improve predictivity.     

Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells

The structural basis of the induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Cvt) in Chinese hamster ovary cells was investigated by the CASE (Computer Automated Structure Evaluation) method, an artificial-intelligence-based system. Using the relevant National Toxicology Program data bases CASE identified a set of structural determinants responsible for the induction of SCE and another one for Cvt. A comparison between the structural determinants associated with SCE and Cvt revealed an overlap of only 22.6%, while the overlap between SCE and the determinants of mutagenicity in Salmonella is 54.5%. This indicates a) that the structural bases of the two phenomena differ and b) that it is likely that SCE, but not Cvt, involves a significant electrophilic/DNA-damaging component.     

Quinoline-induced chromosome aberrations and sister chromatid exchanges in rat liver

Induction of chromosome aberrations and sister chromatid exchanges (SCEs) was studied in hepatocytes of F344 rats exposed in vivo to the hepatocarcinogen quinoline (Q). Hepatocytes were isolated 4–48 hr after a single dose of 200 mg/kg body weight or 24 hr after 28 repeated doses (once a day) of 25–200 mg/kg body weight/day by gastric intubation, and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor. Cells were fixed after a culture period of 48 hr. A single dose of Q induced chromosome aberrations in up to 22% of metaphase cells, and SCEs with a frequency of up to 1.27 per chromosome 12 hr after the dose, while the control values were 1% and 0.63 per chromosome, respectively. Treatment with 28 repeated doses of Q induced significant chromosome aberrations and SCEs dose-dependently. Cytogenetic damage induced in the liver by repeated doses of Q was greater than induced by a single dose. Furthermore, Q induced replicative DNA synthesis in the liver, but failed to induce micronucleus formation in the bone marrow. The noncarcinogen 8-hydroxyquinoline was also examined and found to be essentially non-genotoxic to rat liver. These results show that Q is a genotoxic carcinogen to rat liver and the present method of in vivo cytogenetic assay should be useful for evaluating the genotoxicity of hepatocarcinogens. Environ. Mol. Mutagen. 30:459–467, 1997 © 1997 Wiley-Liss, Inc.     

Diethylstilbestrol-diphosphate induces chromosomal aberrations but not sister chromatid exchanges in murine bone marrow cells in vivo

Diethylstilbestrol diphosphate (DES-dp) clastogenesis was examined in the bone marrow of C57B1/6 male and female mice. Significant and sex-related dose effects were observed for the induction of chromatid-type chromosomal aberrations and for the inhibition of cellular proliferation. Females were more sensitive to the effects of DES-dp than males when assessed for either induced chromosomal aberrations or proliferative inhibition. Contrary to other published results, we did not observe either an increase in sister chromatid exchanges or an increased incidence of aneuploidy. Ovariectomy reduced the ability of DES-dp to inhibit cellular proliferation and decreased the high degree of variability between animals at high doses of DES-dp. The results of our studies show that DES is a clastogenic agent in vivo which may relate to its carcinogenicity.     

The effect of organochlorine compounds on the induction of sister chromatid exchanges in cultured human lymphocytes

In this study, first, we investigated the effect of 7,8-benzoflavone (ANF), mitomycin C (MMC), a well-known genotoxic compound, and ANF plus MMC on the induction of sister chromatid exchanges (SCEs) in human whole-blood cultures. Second, we examined the effect of mixture of organochlorine compounds, which very resembled their contamination of healthy people in its composition, on the induction of SCEs in the same blood culture system in order to clarify their genotoxicity as a whole. The following results were obtained. 1. ANF and MMC significantly enhanced the number of SCEs/cell at the concentrations of 4 x 10(-5) M and 10(-8)M, respectively. When both of the compounds were simultaneously added in the blood cultures, their effects on the induction of SCEs seemed to be additive. 2. Without ANF in the blood culture system, namely, an usual system of the SCEs experiment, we could not find a dose-response relationship between the concentration of the mixture of organochlorine compounds and the induction of SCEs/cell. With ANF, however, we observed a fairly good dose-response relationship between them. 3. In the whole-blood culture system with ANF, we found significantly great number of SCEs/cell at the level of twenty times higher concentration of the organochlorine compounds than the ordinary level. According to the results described above and of our other studies, 50% effective concentration (EC50, about 2 SCEs/cell higher than control SCEs/cell) of the mixture was considered to be about 5 times greater level over the general one.(ABSTRACT TRUNCATED AT 250 WORDS)     

No significant increase in chromosome aberrations and sister chromatid exchanges in cultured human lymphocytes treated with spiramycin.

In this study, the chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) were investigated in human lymphocytes treated with spiramycin antibiotic (trade name, rovamycin). Spiramycin did not induce the CAs and SCEs, and also did not decrease the mitotic index (MI). However, spiramycin decreased the replication index (RI) only at 48 h treatment times.     

Induction of sister chromatid exchanges by coal dust and tobacco snuff extracts in human peripheral lymphocytes

The organic solvent extracts of sub-bituminous coal dust and tobacco snuff, both together and separately, were tested for the induction of sister chromatid exchanges (SCEs) in human peripheral lymphocytes. The results indicate that these extracts induced SCEs, and that when tested together synergistically induced SCEs in two of three donors. Studies with the organic solvent extracts of all five ranks of coal indicate that the extracts of bituminous, lignite, and peat, but not anthracite, induced SCEs. Similar experiments conducted with water extracts show that bituminous, lignite, and peat, but not sub-bituminous extracts, induced SCEs, and that anthracite was equivocal. To determine whether individuals differed in their SCE responses to coal dust extracts, lymphocytes from five donors were tested with organic solvent extracts of bituminous and sub-bituminous coal. An analysis of variance indicates that the SCE response was significantly influenced by the donor (p less than 0.0001) and each of the two coal extracts (p less than 0.0001). From studies of workers occupationally exposed to coal dust, it is known that inhaled coal dust is cleared from the lungs by mucociliary action and introduced into the stomach by swallowing. Coal dust, or coal dust plus snuff, may be responsible for the increased frequency of gastric cancer observed in coal miners. The findings presented here suggest that coal dust, with or without tobacco snuff, may play a role in the elevated incidence of gastric cancer in coal miners. Because water extracts of some ranks of coal induced SCEs, there exists the possibility of adverse environmental effects due to coal leachates.     

Sister chromatid exchanges and chromosomal aberrations induced by mitomycin C in mouse lymphocytes carrying a leukemogenic virus

The induction of chromosomal damage (sister chromatid exchanges (SCEs), chromosomal aberrations, and micronuclei) in T lymphocytes from mouse spleen was analyzed after treatment in vivo with different concentrations of mitomycin C (MMC). Lymphocytes were derived from BALB/Mo mice, which carry an endogenous type C retrovirus (Moloney murine leukemia virus, M-MuLV), and from BALB/c mice (controls, M-MuLV-free). Chromosomal damage was determined in vitro on lymphocytes stimulated with concanavalin A (Con A) and incubated for two generation cycles with bromodeoxyuridine (BUdR). The baseline frequency of SCEs was significantly higher in untreated BALB/Mo than in BALB/c lymphocytes. The frequencies of SCEs were significantly increased by increasing doses of MMC in both BALB/c and BALB/Mo T lymphocytes. Treatment with a low dose of MMC (0.3 mg/kg) produced an additive effect on SCE frequency in BALB/Mo lymphocytes, which was gradually suppressed by increasing the MMC concentration (3-5 mg/kg). Indeed, the levels of SCEs became significantly lower in BALB/Mo than in BALB/c lymphocytes at the highest MMC concentration tested (10 mg/kg), indicating that a negative synergistic effect was eventually produced. Chromosomal aberrations (breaks and total aberrations) were significantly increased by the highest MMC doses (5-10 mg/kg) and were more frequent in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. The frequencies of micronuclei were increased by all MMC doses and were significantly higher in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. These results are referred to interferences of M-MuLV and MMC with the function of enzymes, such as DNA topoisomerases, involved in the mechanism of SCE production.     

Age-related variation in sister chromatid exchanges and cell cycle kinetics in peripheral blood lymphocytes of healthy individuals

Sister chromatid exchanges (SCEs) and cell cycle kinetics were estimated in mitogen stimulated human lymphocytes from a selected group of healthy individuals. Data were examined to evaluate the relationship between SCE frequencies and cell cycle kinetics with donor's age, sex and smoking habit. No regular relationship was observed between the means SCE frequencies and donor's age, although significant differences were observed between the age groups. Correlation of dispersion coefficient (H) of SCE with donor's age were significant in male and female populations. For cell cycle kinetics, a highly significant age-dependent depression in replicative index (RI) was observed. Female donors possessed a slightly higher SCE frequency and RI, although the variations between the two sexes were not significant. Smoking habit resulted in a significant enhancement of SCEs.     

Tissue-specific induction of sister chromatid exchanges by ethyl carbamate in mice

Sister chromatid exchange (SCE) techniques were used to analyze the genetic effects of ethyl carbamate (urethane) in cultured mouse-bone marrow cells, and in several different mouse tissues in vivo. Ethyl carbamate concentrations up to 5.0 mg/ml were ineffective in causing a significant elevation of SCE in vitro. After in vivo drug administration, bone marrow, liver and spermatogonial cells all revealed significant dose-related increases in SCE. Baseline and relative incremental levels of SCE were somatic vs germ tissue-specific. Regenerating liver cells exhibited significantly greater absolute SCE values than all other tissues examined. Marrow cells revealed intermediate values, while germ cells were the least sensitive in SCE responsiveness. Spermatogonia required a fourfold higher dose, over that effective in somatic tissues, to promote an approximate doubling of the baseline SCE level. In vivo SCE analysis affords sensitive risk assessments for different tissues. Thus, this approach should be generally useful for studying compounds with questionable mutagenic potential, and/or those exerting target organ specificities of related biological activity (eg, toxicity, carcinogenesis).     

Evaluation of chromosomal aberrations, micronuclei, and sister chromatid exchanges in hospital workers chronically exposed to ionizing radiation.

Cytogenetic analysis was performed in peripheral blood lymphocytes from hospital workers chronically exposed to ionizing radiation in comparison to matched non-exposed individuals. The accumulated absorbed doses calculated for the radiation workers ranged from 9.5 to 209.4 mSv. The endpoints used were chromosomal aberrations (CA), micronuclei (MN), and sister chromatid exchanges (SCE). The frequencies of CA/100 cells observed for the exposed group were significantly (P=0.018) higher than in the control group: 3.2 and 2.6, respectively. Similarly, the mean numbers of SCE per cell were statistically higher (P=0.025) in the exposed group (6.2) in comparison with the control group (5.8). In the case of micronuclei analysis, no significant (P=0,06) difference between both groups was found, but these data should be cautiously interpreted since an increase in the frequencies of MN was found for radiation workers (3.0 MN/100 cells), compared to the control group (2.6 MN/100 cells) and this increase occur in parallel to CA and SCE frequencies. The difference between the results could be explained by the nature of CA and MN generation. The increased frequencies of CA and SCE in radiation workers indicate the cumulative effect of low-level chronic exposure to ionizing radiation, and the relevance of conducting cytogenetic analysis in parallel to physical dosimetry in the working place.     

广西大厂锡矿区职工外周血淋巴细胞姐妹染色单体交换(SCE)频率、染色体畸变率和微核率的观察

本文分析了38例大厂矿井下矿工、40例井上工作人员和27例非矿区正常人的外周血淋巴细胞SCE频率、染色体畸变率和微核率差异情况,发现井下矿工的SCE频率和染色体畸变率显著高于井上工作人员及非矿区正常人,微核率的差异无显著意义(P>0.05)。结合矿区肺癌流行病学调查结果对比分析,认为井下矿工长期接触的生产性粉尘中可能存在一些致癌物质,导致机体细胞遗传物质受到一定程度损伤。