Potential Mutagenic Agents Research Articles

Evaluation of cell and DNA damage induced by panoramic radiography.

X-rays are potential mutagenic agents that can cause both the gene mutations and chromosomal aberrations. In this study, the micronucleus (MN) test and the comet assay methods are implemented in order to observe the damage that can occur in the cell nucleus and in the structure of DNA of the patients who underwent a panoramic examination. In our study, buccal mucosa swabs were obtained just before the radiography and 2 weeks after the radiography from 30 volunteer patients who had to take radiographs due to dental diagnosis. Changes in the nuclei of 1,000 cells of each swab sample had been counted under a light microscope and recorded. Besides, 100 cells of each other swab samples were analyzed by the comet assay. Comet assay parameters namely tail length and percentage of DNA in tail, which indicate the level of DNA damage were analyzed and compared in both groups. Statistical analysis was performed by using the Statistical Package for the Social Sciences (Version 21). In our study, the results of percentage of DNA in tail and tail length before and after X-ray exposure were statistically significant (P < 0.001). Likewise, increase in the MN frequency observed in buccal mucosa cells after X-ray exposure was found significant (P < 0.001). As a result, panoramic radiographs taken during dental diagnosis and treatment cause cytotoxicity and DNA damage in oral mucosal cells. Panoramic radiographs should be applied only when necessary, using an accurate radiographic technique and radioprotection criteria.

ІI- Potential mutagenic effect of dusting Vicia faba seeds with Malathion 1% powder or fumigating by Phosphine for storage

This work was carried out to evaluate the potential mutagenic effect of the two stored seeds protectant agents “Malathion 1% powder and Phosphine fumes”, commonly used in Egypt, to protect the stored beans from two storage Bruchids pests (Callosobruchus maculates F and C. chinensis L.) after six months of storing of Vicia faba seeds (Var. Giza 716) under treatment with (1, 2 & 4 times the effective concentrations) of each of the two agents. The evaluation took place on: germ cells (meiosis); some quantitative agronomic traits of F1&F2 generation plants and the changes in the storage protein banding pattern of M2 seeds, for each concentration comparing with concomitant negative control. The obtained results emphasized that: “Phosphine fumes” is the more potential mutagenic agent, while “Malathion 1% powder” was the least. So for the need of agriculture Malathion 1% powder can be safely used as seeds’ protectant agent for storage if used in the recommended concentration.

Occupational and life-style factors-acquired mutagenicity in agric-workers of northeastern Brazil.

Pesticides are a complex mixture of chemicals used to protect crops from a number of pests and diseases. They have been considered as potential mutagenic agents. This study aims at evaluation of the mutagenic effect of pesticide exposure to agricultural workers through chromosomal aberrations (CA) and micronucleus (MN) assay in peripheral blood lymphocytes and oral mucosal cells, respectively. The exposed group was consisted with 97 farmers, while the control (un-exposed) group consisted of 55. The results showed a significant (p<0.05) increase in frequency of CA and MN in the exposed group. Both CA and MN profiles were linked to a significant (p<0.05) co-relation with the confounding factors such as smoking habits, alcohol, vegetables, tea/coffee, vitamins, and sweetener consumptions. More cytogenetic events were denoted in smoking and alcohol consumption as well as non-personal protective equipment (non-PPE) and low/no vegetables user farmers. In conclusion, a deficiency of dietary and medicaments-derived antioxidants, while consumption of alcohol and tobacco, as well as effects of radiation, heavy metal poisoning (especially from sweeteners), and non-PPE using habits, may contribute cytogenetic damage to the workers.

English

Most industries are sited with little or no consideration for environmental and social consequences, especially in developing countries. This has led to the discharge of genotoxic chemicals used for many purposes in the manufacturing processes into environmental compartments such as air, water, soil and sediments. Results of the cytotoxic and genotoxic assays of these wastewaters on&nbsp;Allium cepa&nbsp;root tip meristem showed significant reduction of mitotic indices and diverse forms of chromosomal aberrations, cytokinetic failures, micro and multiple nuclei. In Nigeria, the results of diverse assessments of industrial effluents have shown that they are environmental risks and potential mutagenic agents, problems still exist in the enforcement of on ground sound legislative by Federal Ministry of Environment and Federal Environmental Protection Agency. Failure in implementation of sound policies has been identified to be caused by weakness and poor enforcement by the necessary arms of the government, public awareness of international, national and local environmental laws. Legislation and standards that apply to existing and proposed projects are grossly lacking, the absence of mandatory disclosure of information by industries hinders monitoring which is a major problem to compliance and enforcement. Furthermore, there is absence of a legal framework which would ensure that industries comply with the requirement of standing environmental legislation. Any development that does not respect the environment cannot be said to be sustainable. There is therefore the need to integrate the environmental legislatives and environmental impact assessment (EIA) reports in the establishment and consequent monitoring of industries and industrial activities for the establishment and promotion of sustainable development and sound technologies. &nbsp; Key words:&nbsp;Genotoxic,&nbsp;Allium&nbsp;test, industry, legislation, wastewater.

Trisomy 11 and Partial Tandem Duplication of the MLL Gene in a Case of Infant Acute Myeloid Leukemia M0.

Trisomy 11 is uncommon in pediatric acute myeloid leukemia (AML) and molecular studies of AML with trisomy 11 in adult patients have recently revealed high incidence of partial tandem duplication (PTD) of the MLL gene. We report the first case of trisomy 11 and MLL-PTD in a 3 months old girl with AML, the immunophenotype of bone marrow aspirate documented blast cells positive for CD34, CD33, AntiHLA DR, CD117, and MPO <3%, M0 according to FAB classification. No exposure to potential mutagenic agents during pregnancy was documented. The most frequent translocations of MLL, t(4;11) and t(9;11), were investigated by RT-PCR at diagnosis and resulted negative, as well as other genetic abnormalities common in pediatric AML as inv 16, t(8;21), t(15;17), FLT-ITD, D835 mut. Otherwise, interphase FISH analysis, performed with a specific MLL probe, revealed a MLL triple signal (Fig. 1a). Moreover trisomy 11 was confirmed by FISH analysis with a centromeric probe for chromosome 11 (Fig. 1b). RT-PCR analysis revealed PTD of an internal portion of MLL and direct sequencing confirmed the in-frame fusion of exon 6 and exon 2 (Fig. 1c). The self-fused MLL has a duplicated N-terminal region that contains AT hook DNA-binding and DNA methyltransferase motifs. MLL-PTD may involve different exons, and it is known to be associated with a poor prognosis. Even if the oncogenic mechanism of MLL-PTD is not clear yet, several hypothesis suggested a role of DNA binding motifs duplication in the increase of affinity for MLL binding to a target site, or in the separation of autoregolatory domains from their sites of action. Beside its significance as a prognostic marker at diagnosis, MLL-PTD may be a target for PCR-based detection of minimal residual disease in AML patients. [Display omitted]

Culture of pachytene spermatocytes for analysis of meiosis.

An impediment to the investigation of mammalian spermatogenic meiosis has been the lack of an appropriate system for experimental manipulation of meiotic prophase cells. We report here the use of a simple system for the short-term culture of pachytene spermatocytes. We have assayed parameters of cell function pertinent to meiotic prophase, namely chromosome pairing and synapsis. During the culture period of 24-48 hr, cells maintained typical pachytene morphology, chromatin condensation patterns, and chromosome pairing, as assessed by light and electron microscopy. Uridine incorporation, monitored by autoradiography, reflected the chromosomal distribution found in vivo in that the autosomal chromosomes were transcriptionally active, while the sex chromosomes were not. Thus features of chromosome pairing and sex chromatin inactivation are maintained in these cultures. We have conducted experiments to demonstrate that cultured pachytene spermatocytes can be useful for the analysis of agents, some of which may be suspected mutagens, that might affect chromosome structure and function during meiosis. Treatment of cells with actinomycin D revealed a differential effect on chromatin condensation in the autosomes versus the sex chromosomes. Camptothecin, a topoisomerase inhibitor, induced desynapsis of paired chromosomes. Okadaic acid, a phosphatase inhibitor, induced premature metaphase-I condensation of pachytene chromosomes. This last experiment suggests that these cultured cells may be useful for analysis of meiotic cell cycle controls. Taken together, these results demonstrate a culture system that can be useful for analysis of meiotic events as well as in screening for potential mutagenic agents that might affect meiotic chromosome structure and function.

ChemInform Abstract: Oxidation of 8‐Methoxypsoralen (8‐MOP) by Dimethyldioxirane. Evidence for the Formation of a Furocoumarin Epoxide by Methanol Trapping, a Potential Mutagenic Agent.

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Oxidation of 8‐Methoxypsoralen (8‐MOP) by Dimethyldioxirane. Evidence for the Formation of a Furocoumarin Epoxide by Methanol Trapping, a Potential Mutagenic Agent

AbstractThe reaction of 8‐methoxypsoralen (1) with dimethyldioxirane in methanol at 25°C yields the methanol adduct 3, namely the 2,3‐dihydro‐2‐hydroxy‐3,9‐dimethoxy‐7H‐furo[3,2‐g][1]benzopyran‐7‐one, whose structure was unequivocally assigned by means of spectroscopic data. Methanol adduct 3 is produced by dioxirane epoxidation of the furan double bond of 1 to 2 followed by nucleophilic attack by methanol at the benzylically activated C‐3. The direct observation of the 8‐methoxypsoralen epoxide (2) was not possible, because at low temperature (below 0°C) dimethyldioxirane does not epoxidize 1, while at 25°C this labile epoxide decomposes. On the basis of these results, a rational explanation is offered as to the origin of the regioisomeric methanol adduct 5, namely 2,3‐dihydro‐3‐hydroxy‐2,9‐dimethoxy‐7H‐furo[3,2‐g][1]benzopyran‐7‐one, observed in traces (ca. 0.2%), when 1 is treated with sodium hypochlorite and hydrogen peroxide in aqueous methanol.

Studies on the utilization of a plant SCE test in detecting potential mutagenic agents

In this paper a modified procedure for sister-chromatid differentiation in plant cells is reported. Using this procedure some chemicals were tested for SCE induction in Vicia faba, Hordeum vulgare and Secale cereale. The chemicals tested were ethanol, chromium oxide, sodium saccharin, fluorouracil, ascorbic acid (vitamin c), omethoate and phenol. The experimental results showed that most of them induced SCE increases in mouse spleen cells, human lymphocytes and plant cells. The increase of SCEs per cell in plant cells is in agreement with that found in human lymphocytes or in mouse spleen cells. In our opinion, the utilization of SCE in plants is a simple and inexpensive technique for detecting potential mutagenic agents in the environment.

Increased frequency of sister chromatid exchange in workers exposed to high doses of methylmethacrylate

Methylmethacrylate (MMA) is a volatile liquid widely used in the manufacture of acrylic polymers. Apart from its general toxicity (cardiac, respiratory, cutaneous, etc.), MMA is a potential mutagenic agent. Data on the mutagenicity of MMA is available almost exclusively with in vitro systems, thus the demonstration of genetic effects produced by monomeric MMA vapours in exposed workers is valuable additional information. An in vivo sister chromatid exchange (SCE) test was performed using lymphocytes from 31 workers occupationally exposed to MMA and a control group of 31 men whose mean age and smoking habits were similar. Our results indicate that the number of SCE in exposed workers (7.85 +/- 2.66) was not higher than the control group (7.49 +/- 2.33). However, the rate of SCE was significantly higher in the group exposed to MMA at peak concentrations ranging from 114 to 400 p.p.m. A few cells with a large number of SCE, called 'high frequency cells' (HFC), are responsible for this increase.

Sister chromatid exchanges in lymphocytes of dentists and chairside assistants: no indication of a mutagenic effect of exposure to waste nitrous oxide.

Cytogenetic methods are used increasingly for monitoring occupational exposure to potential mutagenic agents. By one such method, the sister chromatid exchange (SCE) test, previous studies of hospital operating room personnel did not indicate any mutagenic effect from exposure to waste anesthetic gases. Dentists and their assistants are exposed to much higher levels of nitrous oxide than hospital personnel, and in studies of dentists it is possible to eliminate bias from concomitant exposure to halogenated anesthetics by including unexposed persons engaged in the same professional activities as the exposed persons. SCE was examined in lymphocytes of venous blood from 38 female dentists and 74 chairside assistants, all working in the Child Dental Service, and 30 male dentists, of whom 23 worked in private practice. From studies of the model y = bo + b1 X age + b2 X cig./day + b3 X hours of exposure to nitrous oxide/week, by multiple linear regression, there was no indication of any influence of exposure to nitrous oxide on SCE. It was concluded that, from the SCE test, there is no indication of a mutagenic effect from exposure to waste nitrous oxide, and that possible health hazards from such exposure would be induced by other effects of nitrous oxide.

Mithramycin- and triethylene melamine- induced sperm abnormalities in Lakeview hamsters.

The sperm abnormality-inducing action of two potential mutagenic agents mithramycin and triethylene melamine (TEM), in inbred Lakeview hamsters was studied and results compared with similar investigations in mouse. Test hamsters received subacute intraperitoneal exposures ranging from 0.01 to 0.25 mg/kg body weight with either agent for 5 consecutive days. Testis weights, epididymal sperm numbers, and body weights were also monitored at weeks 1, 4, and 10 after treatment. Mithramycin-treated hamsters showed 21 times more sperm abnormalities than control (25% vs. 1.2%) whereas TEM elevated sperm abnormalities by eight fold. The frequency and type of aberrant sperm varied with dose and time, being the highest at weeks 1 or 4, rather than week 10, with either agent. Sperm number and testis weights remained depressed considerably from 4 to 10 weeks after treatment with either agent. Body weights in chemically treated hamsters remained within 28% of control for the test period. Even though our findings were in general agreement with those reported for mouse, the magnitude of the response and the stage of spermatogenic sensitivity in the chemical induction of sperm abnormalities in the two species were different.

Some aspects of the detection of potential mutagenic agents in drosophila

The Drosophila system is a valuable test for detecting and characterizing mutagenic agents. Tester strains are available or can be synthesized for determing almost all types of genetical change ranging from gene mutations to chromosome rearrangements in a great variety of cell types of both sexes. Metabolic activation of all groups of indirect mutagens tested so far (aryldialkyltriazenes, cyclophosphamides, nitrosamines, azo-, hydrazo- and azoxyalkanes, aflatoxins, and polycyclic hydrocarbons; about 35 representatives in all), gives strong although indirect support for the considerable metabolizing ability of Drosophila. This capability would be expected from comprehensive biochemical data on bioactivation of foreign compounds in other insects. From a comparison of which types of genetical change are induced at high, low and threshold concentrations, it appears that lethal tests remain the most reliable method for any screening program. Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazene, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome brekage were the only indicator for mutagenic activity. Moreover, for several mono- and polyfunctional agents, the lowest dose which is still genetically active was definitely lowest for recessive lethals when compared with dominant lethals, chromosome rearrangements or loss. If a new mutagen is discovered by a screening procedure using Drosophila, an accurate picture of its ability to cause either or both gene mutations and chromosome aberrations can be drawn. Such work will be valuable in helping to clarify similar problems in mammalian systems. For instance, it was important to learn that mutagens of the nitrosamine type apparently fail to produce breakage events in Drosophila. Similarly, three cyclophosphamides appeared not to have chromosome breaking ability. However, from a more detailed study, in which a series of concentrations was used, it became obvious that a penetration effect or, more likely, a rate-limiting factor in bioactivation, was the cause of the negative results obtained with these agents.

Some aspects of the detection of potential mutagenic agents in drosophila

The Drosophila system is a valuable test for detecting and characterizing mutagenic agents. Tester strains are available or can be synthesized for determing almost all types of genetical change ranging from gene mutations to chromosome rearrangements in a great variety of cell types of both sexes. Metabolic activation of all groups of indirect mutagens tested so far (aryldialkyltriazenes, cyclophosphamides, nitrosamines, azo-, hydrazo- and azoxyalkanes, aflatoxins, and polycyclic hydrocarbons; about 35 representatives in all), gives strong although indirect support for the considerable metabolizing ability of Drosophila. This capability would be expected from comprehensive biochemical data on bioactivation of foreign compounds in other insects. From a comparison of which types of genetical change are induced at high, low and threshold concentrations, it appears that lethal tests remain the most reliable method for any screening program. Mutagenic agents such as diethylnitrosamine, hycanthone and certain triazene, which are highly efficient in the induction of recessive lethals (gene mutations and/or deficiencies), would not have been detected in Drosophila if chromosome brekage were the only indicator for mutagenic activity. Moreover, for several mono- and polyfunctional agents, the lowest dose which is still genetically active was definitely lowest for recessive lethals when compared with dominant lethals, chromosome rearrangements or loss. If a new mutagen is discovered by a screening procedure using Drosophila, an accurate picture of its ability to cause either or both gene mutations and chromosome aberrations can be drawn. Such work will be valuable in helping to clarify similar problems in mammalian systems. For instance, it was important to learn that mutagens of the nitrosamine type apparently fail to produce breakage events in Drosophila. Similarly, three cyclophosphamides appeared not to have chromosome breaking ability. However, from a more detailed study, in which a series of concentrations was used, it became obvious that a penetration effect or, more likely, a rate-limiting factor in bioactivation, was the cause of the negative results obtained with these agents.