Number Of Structural Chromosomal Aberrations Research Articles

Study of the toxic and genotoxic activity of water of lake Kolsai, located on the territory of the Almaty region of the Republic of Kazakhstan

An important step in assessing the state of natural environment is the identification of various environmentally hazardous factors that possess toxic, genotoxic and mutagenic activity. The appearance in the environment of a new pollutants and an increase in the concentration of already present physicochemical components that exhibit toxic and genotoxic properties contribute to environmental mutational load on biota. In recent decades, due to the intensification of economic activity and the development of the tourism sector, the anthropogenic load has significantly increased not only on terrestrial, in particular mountain ecosystems, but also on natural water reservoirs. In this regard, the purpose of this study was to investigate the genotoxic, mutagenic and toxic activity of surface water of the freshwater lake Nizhny Kolsai, located on the territory of national park "Kolsai kolderi" in the Kegen district of the Almaty region, Republic of Kazakhstan. For the first time, using a number of test systems (DNA comet method, cytogenetic test for accounting for chromosomal aberrations and biochemical analysis of lipid peroxidation products), water samples taken in 2018 and 2022 (spring-summer period) were studied at the Mus musculus model facility. It was found that water samples induced DNA breaks in cells of bone marrow and spleen of experimental mice, the level of which was significantly higher than in intact animals (p<0.001). Cytogenetic analysis of the bone marrow of mice treated with lake water also showed a statistically significant increase in the frequency of aberrant cells and the number of structural chromosome aberrations per 100 metaphases (p<0.05). A biochemical study of lipid peroxidation products (LPO) in the liver of experimental animals also revealed a statistically significant (p<0.05) increase in the level of lipid hydroperoxide (HPL) and malondialdehyde (MDA). The results obtained indicate the presence in the studied natural surface waters of chemicals with genotoxic, mutagenic and toxic activity. Key words: natural surface waters, genotoxicity, organ specificity, chromosomal aberrations, comet DNA assay.

Genotoxicity evaluation of Hwanglyeonhaedok-tang, an herbal formula

Ethnopharmacological relevanceHwanglyeonhaedok-tang (Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for the treatment of inflammatory, gastrointestinal and cardiovascular diseases. PurposeThe purpose of this study was to evaluate the genotoxic potential of Hwanglyeonhaedok-tang water extract (HLHDT). MethodsA genotoxicity test was conducted using a bacterial reverse mutation test (Ames test), an in vitro chromosome aberration test using Chinese hamster lung cells, and an in vivo micronucleus test using ICR mouse bone marrow. ResultsIn the Ames test, which used different Salmonella typhimurium (S. typhimurium) and Escherichia coli (E. coli) strains, HLHDT did not increase the number of revertant colonies of S. typhimurium strains TA98, TA100 and TA1535 as well as E. coli strains with or without S9 mix. However, the number of revertant colonies with the S. typhimurium TA1537 strain and S9 mix increased in a dose-dependent manner. The chromosome aberration test showed that HLHDT did not increase the number of structural or numerical chromosome aberrations in a short-period test (6h) with S9 mix. By contrast, HLHDT significantly increased the number of structural chromosome aberrations in a short-period (6h) or continuous (22h) test without S9 mix. In the micronucleus test, no significant increase was observed in micronucleated polychromatic erythrocytes, and no significant decrease was observed in polychromatic to total erythrocytes. ConclusionsThese results indicate that HLHDT might be genotoxic, based on both the Ames and chromosome aberration tests. Therefore, further in vivo studies will be needed to define the mechanism of this genotoxicity.

Genotoxicity study of silver nanoparticles in bone marrow cells of Sprague–Dawley rats

The antimicrobial properties of silver nanoparticles (Ag-NPs) have resulted in their extensive application in consumer and health care products. Although Ag-NPs have great potential benefits, their side effects are unknown and seem inevitable due to their ability to reach the nucleus and damage genetic material. This study aimed to determine genotoxic potential of Ag-NPs using mitotic index (MI), DNA damage (comet assay), structural chromosome aberrations (SCA), micronuclei (MN) formation as genetic endpoints and induction of reactive oxygen species (ROS) as oxidative stress endpoint in bone marrow of Sprague–Dawley rats. Four groups of five male rats were orally administered Ag-NPs, once a day for five days with doses of 5, 25, 50, 100, mg/Kg. A control group was also made of five rats. Bone marrow samples were collected 24 h after the last treatment following standard protocols. Ag-NPs exposure significantly increased (p < 0.05) the induction of ROS, number of SCA, the frequency of micro-nucleated cells, damaged the DNA and decreased the mitotic index compared to negative control. The results suggest that Ag-NPs may have the potential to induce oxidative stress mediated genotoxicity in rats. Further characterization of their genotoxicity and also their potential health implications should be monitored regularly.

Cytogenetic evaluation of functionalized single-walled carbon nanotube in mice bone marrow cells.

With their unique structure and physicochemical properties, single\-walled carbon nanotubes (SWCNTs) have many potential new applications in medicine and industry. However, there is lack of detailed information concerning their impact on human health and the environment. The aim of this study was to assess the effects, after intraperitoneal injection of functionalized SWCNTs (f-SWCNT) on the induction of reactive oxygen species (ROS), frequency of structural chromosomal aberrations (SCA), frequency of micronuclei induction, mitotic index, and DNA damage in Swiss-Webster mice. Three doses of f-SWCNTs (0.25, 0.5, and 0.75 mg/kg) and two controls (negative and positive) were administered to mice, once a day for 5 days. Bone marrow and peripheral blood samples were collected 24 h after the last treatment following standard protocols. F-SWCNT exposure significantly enhanced ROS, increased (p < 0.05) the number of SCA and the frequency of micronucleated cells, increased DNA damage, and decreased the mitotic index in exposed groups compared to negative control. The scientific findings reported here suggest that purified f-SWCNT have the potential to induce oxidative stress mediated genotoxicity in Swiss-Webster mice at higher level of exposure. Further characterization of their systemic toxicity, genotoxicity, and carcinogenicity is also essential. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1091-1102, 2016.

A rare polymorphic variant of NBS1 reduces DNA repair activity and elevates chromosomal instability.

Failure to expeditiously repair DNA at sites of double-strand breaks (DSB) ultimately is an important etiologic factor in cancer development. NBS1 plays an important role in the cellular response to DSB damage. A rare polymorphic variant of NBS1 that resulted in an isoleucine to valine substitution at amino acid position 171 (I171V) was first identified in childhood acute lymphoblastic leukemia. This polymorphic variant is located in the N-terminal region that interacts with other DNA repair factors. In earlier work, we had identified a remarkable number of structural chromosomal aberrations in a patient with pediatric aplastic anemia with a homozygous polymorphic variant of NBS1-I171V; however, it was unclear whether this variant affected DSB repair activity or chromosomal instability. In this report, we demonstrate that NBS1-I171V reduces DSB repair activity through a loss of association with the DNA repair factor MDC1. Furthermore, we found that heterozygosity in this polymorphic variant was associated with breast cancer risk. Finally, we showed that this variant exerted a dominant-negative effect on wild-type NBS1, attenuating DSB repair efficiency and elevating chromosomal instability. Our findings offer evidence that the failure of DNA repair leading to chromosomal instability has a causal impact on the risk of breast cancer development.

The effects of biological and life-style factors on baseline frequencies of chromosome aberrations in human lymphocytes

Objective: This study investigated the influence of sex and ageing on chromosomal damage and the role of life-style habits on the frequency of chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) of healthy Bosnian subjects. Materials and Methods: Peripheral blood samples were obtained from 100 healthy, unrelated individuals in Bosnia and Herzegovina during 2010 and 2011. Chromosome preparations were made by dropping and air drying and slides were stained with 10% Giemsa solution (pH 6.8). The cytogenetic analysis was carried out in a cytogenetic laboratory in the Department of Biology of the Faculty of Science in Sarajevo. The category of total structural CAs was sub classified as chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs) while the category of total numerical CAs was sub classified as aneuploid and polyploid mitoses. All statistical analyses were carried out using Microsoft Excel 2010 (Microsoft Corporation) and the Windows Kwikstat Winks SDA 7.0.2 statistical software package (Texa Soft Cedar Hill, Texas). Results: Cytogenetic analysis revealed the average number of structural CAs was 2.84 and of numerical CAs was 9.56. There was a significant increase in the frequency of chromosome-type aberrations (1.92) compared with chromatid-type aberrations (CTAs) (0.92) and a significant increase in the frequency of aneuploid (8.83) compared with polyploid (0.73) mitoses. Significant positive correlations between age and CTAs in human PBLs were also demonstrated. Additional statistical analysis showed that ageing increase number of numerical CAs in lymphocytes of drinkers. The frequency of structural CAs of females exposed to radiation was significantly greater than in males. Analysis indicates the presence of a positive association between CAs and smoking in younger subjects but a negative correlation between aberrant cells frequencies and alcohol in older drinkers. Conclusion: The results of the study support the conclusion that sex and age, together with life-style habits of individuals as confounding factors can affect spontaneous frequency of CAs especially to CTAs in PBLs that are a biomarker of cancer risk.

Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague–Dawley rats

Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague–Dawley rats. Four groups of six male rats, each weighing approximately 60±2g, were injected intraperitoneally, once a day for 5days with doses of 5, 10, 15, 20mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase–glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase–glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague–Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

Evaluation of genotoxicity of multi-walled carbon nanotubes in a battery of in vitro and in vivo assays

The genotoxic potential of two products of multi-walled carbon nanotubes (coded as N-MWCNTs, diameter of 44nm/BET surface area of 69m2/g and MWNT-7, diameter of 70nm/BET surface area of 23m2/g) was evaluated using a battery of genotoxicity assays, comprising a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and a mammalian erythrocytes micronucleus test. Neither type exerted mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, or in Escherichia coli WP2uvrA, in the absence or presence of metabolic activation. The products of MWCNTs did not increase the number of structural chromosomal aberrations either, regardless of metabolic activation, though they increased the number of numerical chromosomal aberrations, one slightly and the other distinctly, in the absence of metabolic activation. In ICR mice, the two products did not affect the proportion of immature erythrocytes, the total proportion of erythrocytes, or the number of micronuclei in immature erythrocytes.

Evaluation of mutagenic effect of two antiobesity drugs on mice’s genetic materials

Obesity is a complex, multifactorial disease that, similarly to high blood pressure and diabetes, frequently requires pharmacological treatment with long-term use, suggesting that pattern of use could increase the rates of genetic damage. Among antiobesity drugs, meridia and orlistat act with completely different mechanisms of action. This study aimed to evaluate the mutagenic effect of meridia and orlistat on genetic material of mice by cytogenetic analysis, which included the micronucleus test and chromosomal aberration assay at two doses comparable to propose human therapeutic and double therapeutic doses. Results revealed that the total number of structural chromosomal aberrations in bone marrow cells, with gap, was significantly increased for the two drugs at therapeutic doses. The structural chromosomal aberrations involved breaks, gaps, deletions and fragments, and centric fusion. Chromosomal deletions and fragments were the most frequently increased types of structural chromosomal aberrations. At double therapeutic doses, the treated animals showed a high significant increase of total structural chromosomal aberrations with and without gaps for the two drugs. The frequency of micronucleus in mice treated with therapeutic doses was significantly increased for both drugs. The treated animals at double therapeutic doses showed a positive response for both drugs. In conclusion, treatment with these two drugs at therapeutic doses should be taken under precaution and contraindicated at double therapeutic doses, because the cytogenetic analysis of meridia and orlistat showed an adverse effect on genetic materials at therapeutic doses and a mutagenic effect at double therapeutic doses.

Cytogenetic evaluation of malathion-induced toxicity in Sprague-Dawley rats

Malathion is a well known pesticide and is commonly used in many agricultural and non-agricultural settings. Its toxicity has been attributed primarily to the accumulation of acetylcholine (Ach) at nerve junctions, due to the inhibition of acetylcholinesterase (AChE), and consequently overstimulation of the nicotinic and muscarinic receptors. However, the genotoxicity of malathion has not been adequately studied; published studies suggest a weak interaction with the genetic material. In the present study, we investigated the genotoxic potential of malathion in bone marrow cells and peripheral blood obtained from Sprague-Dawley rats using chromosomal aberrations (CAs), mitotic index (MI), and DNA damage as toxicological endpoints. Four groups of four male rats, each weighing approximately 60±2g, were injected intraperitoneally (i.p.) once a day for five days with doses of 2.5, 5, 10, and 20mg/kg body weight (BW) of malathion dissolved in 1% DMSO. The control group was made up of four animals injected with 1% DMSO. All the animals were sacrificed 24h after the fifth day treatment. Chromosome preparations were obtained from bone marrow cells following standard protocols. DNA damage in peripheral blood leukocytes was determined using alkaline single-cell gel electrophoresis (comet assay). Malathion exposure significantly increased the number of structural chromosomal aberrations (CAs) and the percentages of DNA damage, and decreased the mitotic index (MI) in treated groups when compared with the control group. Our results demonstrate that malathion has a clastogenic/genotoxic potential as measured by the bone marrow CA and comet assay in Sprague-Dawley rats.

Comparative study of the clastogenicity of functionalized and nonfunctionalized multiwalled carbon nanotubes in bone marrow cells of Swiss‐Webster mice

The development of nanotechnologies may lead to environmental release of nanomaterials that are potentially harmful to human health. Among the nanomaterials, multiwalled carbon nanotubes (MWCNTs) are already commercialized in various products which can be in direct contact with populations. However, few studies address their potential toxicity. Although a few reports on the cytotoxicity of carbon nanotubes (CNTs) have been published, very little is known about their toxicity or genotoxicity in mammalian cells. We have for the first time compared the clastogenic/genotoxic potential of functionalized and nonfunctionalized MWCNTs in bone marrow cells of Swiss-Webster mice; using mitotic index (MI), chromosome aberrations (CA), micronuclei (MN) formation, and DNA damage in leukocytes as toxicologic endpoints. Six groups of five male mice, each weighing ∼30 ± 2 g, were administered intraperitoneally, once a day for five days with doses of 0.25, 0.5, 0.75, mg/kg body weight (BW) of functionalized and nonfunctionalized MWCNTs. Four vehicle control groups (negative) and a positive control group (carbon black) were also made of 5 mice each. Chromosome and micronuclei from bone marrow cells and comet slides from leukocytes were examined following standard protocols. The results demonstrated that MWCNTs exposure significantly increased (P < 0.05) the number of structural chromosomal aberrations, the frequency of micronucleated cells and the level of DNA damage, and decreased the mitotic index in treated groups compared to control groups. MWCNTs were shown to be toxic at sufficiently high concentrations, however purified functionalized MWCNTs had a higher clastogenic/genotoxic potential compared to nonfunctionalized form of MWCNT. The results of our study suggest that exposure to MWCNT has the potential to cause genetic damage. Hence, careful monitoring should be done with respect to designing/synthesizing biocompatible carbon nanomaterials. Further characterization of their systemic toxicity, genotoxicity and carcinogenicity is also essential.

Protein-energy malnutrition contributes to increased structural chromosomal alteration frequencies in Argentinean children

The relationship between protein-energy malnutrition and genetic damage has been studied in human beings and laboratory animals, but results are still conflicting. The aim of the present study was to assess the induction of structural chromosomal aberrations in peripheral blood lymphocytes of children with primary protein-energy malnutrition. A case-control study was performed. Samples were obtained from 25 primary malnourished infants (mean age, 22 months; range, 1-66 months). The control group consisted of 25 eutrophic children from the same population who were matched 1:1 by age and sex. Anthropometric and clinic evaluations were performed to assess nutritional condition. Before blood collection, we interviewed each individual's parent to complete a semi-structural survey specifying age, dietary habits, viral or bacterial diseases; previous exposure to diagnostic x-rays; and use of therapeutic drugs. After 48 hours, 100 cultured lymphocytes were analyzed per patient. Statistical analysis was performed using the Epi Dat 3.0 program (P < or = .05). The chromosomal aberration frequency was nearly 7 times higher in malnourished infants than in controls (14.61% vs 2.2%, respectively). This difference was statistically significant (P < .001) and may be explained by the occurrence of achromatic lesions, breaks, and telomeric associations. DNA damage could be attributed to several factors: severe deficiency of essential nutrients (ie zinc, iron, and vitamin A) required in the synthesis of DNA maintenance factors; deterioration of repair mechanisms allowing the persistence of an unusually high number of structural chromosomal aberrations; and/or the absence of specific factors needed to protect the cell against oxidative DNA damage.

Essential Role for Nuclear PTEN in Maintaining Chromosomal Integrity

A broad spectrum of mutations in PTEN, encoding a lipid phosphatase that inactivates the P13-K/AKT pathway, is found associated with primary tumors. Some of these mutations occur outside the phosphatase domain, suggesting that additional activities of PTEN function in tumor suppression. We report a nuclear function for PTEN in controlling chromosomal integrity. Disruption of Pten leads to extensive centromere breakage and chromosomal translocations. PTEN was found localized at centromeres and physically associated with CENP-C, an integral component of the kinetochore. C-terminal PTEN mutants disrupt the association of PTEN with centromeres and cause centromeric instability. Furthermore, Pten null cells exhibit spontaneous DNA double-strand breaks (DSBs). We show that PTEN acts on chromatin and regulates expression of Rad51, which reduces the incidence of spontaneous DSBs. Our results demonstrate that PTEN plays a fundamental role in the maintenance of chromosomal stability through the physical interaction with centromeres and control of DNA repair. We propose that PTEN acts as a guardian of genome integrity.

Cytogenetic evaluation of arsenic trioxide toxicity in Sprague–Dawley rats

Acute exposure to arsenic trioxide has been reported to induce death and/or multiple organ damage with symptoms including nausea, vomiting, diarrhea, gastrointestinal hemorrhage, cerebral edema, tachycardia, dysrhythmias and hypovolemic shock. Its toxic effects are due to its ability to bind to sulfhydryl groups of proteins and to inhibit energy production. Although the chronic exposure to arsenic trioxide has been linked to various types of cancer, such as skin, liver, lung, bladder and kidney neoplasms, studies of its carcinogenic potential in animals have not been conclusive. In this study, we investigated the genotoxic potential of arsenic trioxide in bone-marrow cells obtained from Sprague–Dawley rats; using chromosomal aberrations (CA), mitotic index (MI) and micronuclei (MN) formation as the toxicological endpoints. Four groups of six male rats each, weighing approximately 60 ± 2 g per rat, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15 and 20 mg/kg body weight (BW) of arsenic trioxide dissolved in distilled water. A control group was also made of six animals injected with distilled water without chemical. All the animals were sacrificed at the end of the treatment period. Chromosome and micronuclei preparation was obtained from bone-marrow cells following standard protocols. Arsenic trioxide exposure significantly increased the number of structural chromosomal aberrations, the frequency of micronucleated cells and decreased the mitotic index in treated groups when compared with the control group. Our results demonstrate that arsenic trioxide has a clastogenic/genotoxic potential as measured by the bone-marrow CA and MN tests in Sprague–Dawley rats.

Cytogenetic and Hematological Effects of the Antibiotic Chloramphenicol on Calves

The present study demonstrated the cytogenetic and hematological effects of the antibiotic chloramphenicol in blood cultures of calves, at 4 days and 3 weeks after stoppage of injection with chloramphenicol by the minimal therapeutic dose (once a day for 4 successive days).The different types of chromosomal aberrations including breaks, gaps, deletions and fragments were increased in blood cultures after injection with chloramphenicol at significant levels ranging from p<0.05 to p<0.01. The total number of structural chromosomal aberrations was increased at highly significant level p<0.001 when compared with control.The frequencies of sister chromatid exchanges in blood cultures of calves after the injection with chloramphenicol were significantly increased, whereas the mitotic index was decreased at significant levels ranging from p<0.01 to p<0.001.The hematological analysis showed that there is no change in hemoglobin concentration after injection with chloramphenicol. Leucocytosis was shown only at 4 days after the stoppage of injection with chloramphenicol, whereas the lymphopenia and the neutrophilia were shown at 21 days after the stoppage of injection.

Cytogenetic effects of lambda-cyhalothrin on Wistar rat bone marrow

In this study, the genotoxic and cytotoxic potential of lambda-cyhalothrin (LCT), a synthetic pyrethroid insecticide, was investigated in Wistar rat bone-marrow cells, using the structural chromosomal aberration (SCA) and micronucleus (MN) test systems. LCT was administrated to adult female albino rats as repeated i.p. doses of 6.12, 3.06, 0.8 mg/kg BW for 13 days at 48 h intervals. Mitomycin C (MMC) was used as a positive control (2 mg/kg BW). All the doses of LCT increased the number of structural chromosomal aberrations and the frequency of micronucleated erythrocytes, compared with the control group. It was also observed that LCT caused a significant decrease in the number of polychromatic erythrocytes. Our results demonstrate that LCT has a clastogenic/genotoxic potential as measured by the bone marrow SCA and MN tests in Wistar rats.

Acute cytogenetic effects of antineoplastic drugs on peripheral blood lymphocytes in cancer patients chromosome aberrations and micronuclei.

The aim of the present study was to evaluate the individual sensitivity of cancer patients to different antineoplastic drugs administered in standard protocols by assessing their acute cytogenetic effects on peripheral blood lymphocytes. In 12 patients undergoing cancer chemotherapy, acute cytogenetic effects on peripheral blood lymphocytes were evaluated by analysis of structural chromosome aberrations and micronuclei. All patients were given antineoplastic drugs, mainly as polychemotherapy. The frequencies of both cytogenetic biomarkers determined after the first chemotherapy cycle were compared with their pre-treatment (baseline) values. All chemotherapy protocols employed induced clear cytogenetic effects in both tests studied. The results obtained indicate interindividual variations between cytogenetic damage in peripheral blood lymphocytes among cancer patients. Statistically significant increases in the total number of structural chromosome aberrations and micronuclei in lymphocytes analyzed after chemotherapy compared to pre-therapy samples were observed in almost all patients studied. The highest level of chromosome damage as well as the highest incidence of micronuclei was observed following administration of the ACOP protocol (adriamycin, cyclophosphamide and vincristine). The proportions of signal-positive and signal-negative micronuclei were evaluated using DAPI staining, while silver staining revealed Ag-NOR+ and Ag-NOR- micronuclei. In some patients the incidence of signal-positive and Ag-NOR+ micronuclei after treatment was increased, indicating a more pronounced susceptibility of particular chromosomes to damage caused by antineoplastic drugs. With regard to the results obtained we may conclude that both parameters used in the present study on peripheral lymphocytes are sensitive biomarkers and can be successfully employed for biomonitoring of acute cytogenetic effects induced by antineoplastic drugs in standard clinical protocols for cancer treatment.

Protective role of soybean feeding against the cytogenetical and histopathological effects of dibutylamine and sodium nitrate on bone marrow and liver of mice

The protective role of soybean feeding against the cytogenetic and histopathologic effects of the nitrosamine precursors sodium nitrate and dibutylamine was evaluated. Treated animals were killed every 3 months, over a period of 15 months, and bone marrow cells were prepared for cytogenetic studies and livers for histopathological observations. Structural chromosomal aberrations and mitotic indices increaseda after treatment with the nitrosamine precursors for all tested times. Livers were within the normal appearance during the first 6 months. After that a mild, moderate, marked dysplasia with lymphocytic infiltration, fatty vacuolation and liver atrophy was observed. Soybean coadministered with the nitrosamine precursors reduced the number of structural chromosomal aberrations. Mitotic indices decreased at all tested groups but still higher than the control level. A marked reduction in dysplastic features in the liver cells was observed. In conclusion, the cytogenetic and histopathologic results of this study strongly support the protective role of soybean against the genotoxic and carcinogenic action of nitrosomine formed in vivo from its precursors.

Pyrrolizidine alkaloids with chromosome-damaging effects on human lymphocytes in vitro

The pyrrolizidine alkaloids senkirkine and tussilagine which occur in the aerial parts of the medicinal plant Tussilago farfara were investigated for their ability to induce chromosome damage in human lymphocytes in vitro. Up to concentrations of 1000 µM the two alkaloids did not enhance the number of structural chromosome aberrations. In contrast, heliotrine, a pyrrolizidine alkaloid used for comparison, induced chromosomal aberrations when tested at a concentration of 100 µM. Additionally, heliotrine was capable to damage the chromosomes of unstimulated lymphocytes, i. e. G0-phase lymphocytes.

Effect of human leukocyte interferon on human lymphocytes in vitro: cytogenetic studies

Mitogen-stimulated lymphocytes from 8 healthy donors were exposed to interferon, and cytogenetic studies were performed. The response of lymphocytes to the mitogens phytohemagglutinin (PHA), concanavalin A (con A) and pokeweed mitogen (PWM) was inhibited by interferon, whereas an increased number of structural chromosomal aberrations was not detected. Further investigations of the cytogenetic effects of interferon are needed.