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PubMed1997

Modulating effects of flavonoids on food mutagens in human blood and sperm samples in the comet assay.

The flavonoids silymarin, myricetin, quercetin, kaempferol, rutin, and kaempferol-3-rutinoside have been examined in combination with the food mutagens 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp) and 2-amino-3-methylimidazo-4,5-f)quinoline (IQ) in the Comet assay in human lymphocytes from donors A and B and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in human lymphocytes and sperm over a similar dose range in the absence of metabolic activation. Only quercetin and kaempferol were examined in blood with metabolic activation, but there was no difference in response to that obtained without activation. In the blood there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm this was also the case with silymarin and myricetin. With kaempferol there was no antigenotoxic effect and quercetin protected below baseline levels. Since the effects were observed in lymphocytes and sperm over a similar dose range, it would suggest that the Comet assay responses occur in somatic and germ cells in a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.

Adult↗
PubMed1998

Comparison between pulsed-field gel electrophoresis and the comet assay as predictive assays for radiosensitivity in fibroblasts.

The radiosensitivity of skin fibroblasts derived from patients as measured in vitro by a clonogenic survival assay appears to correlate with the risk of developing severe late reactions to radiation. Unfortunately, these assays are clinically impractical as a predictive test for radiosensitivity. The purpose of this study was to assess the utility of two possible surrogate assays for radiosensitivity, pulsed-field gel electrophoresis (PFGE) and single-cell gel electrophoresis (comet assay), both of which can be used to measure DNA double-strand breaks. Twenty-three nontransformed human fibroblast cell lines exhibiting a range of radiosensitivities were studied with both of these assays. The results were correlated with measurements of radiosensitivity obtained as part of a larger study examining the correlation between cellular radiosensitivity and clinical response. [2-(14)C]Thymidine-labeled confluent cultures were irradiated at 1.0 Gy/min with doses of 0 to 150 Gy. After allowing 4 h for repair at 37 degrees C, cells were trypsinized and aliquots were used for preparing slides for the comet assay. After neutral lysis and electrophoresis, the slides were stained with ethidium bromide and 50 comet moments were measured for each dose. The remainder of the cells were formed into agarose plugs and, after neutral lysis, were subjected to PFGE. The fraction of activity released (FAR) from the well was measured by scintillation counting of appropriate segments of each gel lane. Cellular radiosensitivity was measured with a standard clonogenic assay at a low dose rate of 1.2 cGy/min, and the dose that resulted in a surviving fraction of 0.01 (D0.01) was calculated. The slope of the plot of comet moment as a function of dose for each cell line did not correlate with D0.01 (R = 0.36, P > 0.1). In contrast, the slope of the FAR as a function of dose had a weak inverse correlation with D0.01 (R = 0.43 and P = 0.05) such that the more radiosensitive cell lines exhibited a steeper dose response for FAR. Although the correlation between the slope of the dose response for FAR and D0.01 was weak, refinement of the PFGE technique may provide a potentially useful predictive assay for radiosensitivity.

Breast↗
PubMed2006

Fourth International Workgroup on Genotoxicity testing: results of the in vivo Comet assay workgroup.

As part of the Fourth International Workshop on Genotoxicity Testing (IWGT), held 9-10 September 2005 in San Francisco, California, an expert working group on the Comet assay was convened to review and discuss some of the procedures and methods recommended in previous documents. Particular attention was directed at the in vivo rodent, alkaline (pH >13) version of the assay. The aim was to review those protocol areas which were unclear or which required more detail in order to produce a standardized protocol with maximum acceptability by international regulatory agencies. The areas covered were: number of dose levels required, cell isolation techniques, measures of cytotoxicity, scoring of comets (i.e., manually or by image analysis), and the need for historical negative/positive control data. It was decided that a single limit dose was not sufficient although the required number of dose levels was not stipulated. The method of isolating cells was thought not to have a qualitative effect on the assay but more data were needed before a conclusion could be drawn. Concurrent measures of cytotoxicity were required with histopathological examination of tissues for necrosis or apoptosis as the "Gold Standard". As for analysing the comets, the consensus was that image analysis was preferred but not required. Finally, the minimal number of studies required to generate a historical positive or negative control database was not defined; rather the emphasis was placed on demonstrating the stability of the negative/positive control data. It was also agreed that a minimum reporting standard would be developed which would be consistent with OECD in vivo genotoxicity test method guidelines.

Animals↗
PubMed2005

Heterogeneity in DNA damage using the comet assay.

The single-cell gel electrophoresis or "comet" assay was developed many years ago to analyze DNA damage in individual cells. It is a powerful and versatile technique that relies on microscopic visualization or imaging of DNA after single cells are embedded in agarose, lysed, and electrophoresed. In addition, the basic methodology has been extended to permit the detection of a variety of classes of DNA damage with good sensitivity in virtually any single-cell type. A unique but understudied property of the comet assay is its ability to detect and quantify cellular heterogeneity in response to DNA-damaging agents. This review outlines the considerations in producing and analyzing comet data when heterogeneity in induction of or cellular response to DNA damage is the major consideration. Examples are presented to emphasize the heterogeneity of tumor response to ionizing radiation and cytotoxic drugs.

Animals↗
PubMed2002

New measure of DNA repair in the single-cell gel electrophoresis (comet) assay.

Since its introduction by Ostling and Johanson [1984; Biochem Biophys Res Commun 123:291-298] and independent modifications by Singh et al. [1990; Exp Cell Res 175:184-191] and Olive et al. [1988; Radiat Res 112:86-94], the comet assay has been widely used in genetic toxicology, environmental biomonitoring, molecular and human epidemiology, and clinical investigations. There are still several issues to be resolved before the comet assay is accepted as a standard assay for detecting DNA damage and repair in a single cell. One of the major issues is the proper quantification of DNA damage/repair. The aim of this article is to develop a new quantitative measure of DNA damage/repair which is represented in the dose-time-response surface. We propose to use the second derivative (2D) of the dose-time-response surface for measuring DNA repair activity. This approach enables us to represent the DNA repair activity of cells exposed to a DNA-damaging agent with a single number by combining all the information of a dose-time-response experiment. The computation procedure includes the application of linear regression. An SAS/AF-based program, "Comet Assay," was developed for this computation and is freely available on the Internet. We considered the response of each of four DNA damage parameters: tail moment, tail length, tail DNA, and tail inertia for constructing the dose-time-response surface. Using data from 25 patients, we observed that 2Ds based on tail moment and tail DNA were highly correlated and that tail inertia might provide information on a somewhat different aspect of DNA damage/repair.

Breast Neoplasms↗
PubMed2004

Fish as bioindicators to assess the effects of pollution in two southern Brazilian rivers using the Comet assay and micronucleus test.

Industrial effluents, agricultural runoff, and municipal wastewaters contain unknown substances and complex mixtures that are released into the environment and can lead to contamination of surface and subsurface waters. In the present report, we have used the alkaline Comet assay and the micronucleus (MN) test to detect the genotoxicity due to multiple sources of pollution in the peripheral blood of two native estuarine fish (mullet and sea catfish) and evaluated possible interactive genotoxic effects from multiple contaminants and the seasonal variation of the genotoxicity. Mullet and sea catfish were captured in the Tramandai and Mampituba Rivers in the southern Brazilian state of Rio Grande do Sul. Reference animals were obtained from the Armazem lagoon. Fish captured in the two estuaries during the four seasons over a period of 2 years had increased levels of DNA damage and MN frequencies relative to the reference fish. In general, the alkaline Comet assay was more sensitive to the genotoxicity of the river contaminants than the MN test. The Comet assay demonstrated significant differences in fish captured at different seasons and at the two river sites, while the MN test showed significant differences only for the annual average for mullet from both sites and fish from the control site. The increases in DNA damage appear to be related to the increase in the number of people in the towns close to the study areas during the warm spring and summer seasons. Although no specific cause-effect relationships were established, comparison of the chemical contaminants and physical variations in the rivers with the genotoxicity data indicate that there may be some association between hydrocarbons, metals, pH, and water temperature and the level of damaged cells observed in mullet and sea catfish from the Tramandai and Mampituba estuaries.

Animals↗
PubMed2005

DNA damage in lymphocytes of rural Indian women exposed to biomass fuel smoke as assessed by the Comet assay.

The Comet assay has found wide acceptance in monitoring human genotoxicity caused by lifestyle and occupational and environmental factors. In the present study, we have used the Comet assay to measure the DNA damage in a population of rural Indian women cooking with biomass fuels (BMFs; fire wood and cow dung cakes). Out of 144 volunteers, 70 used BMFs for domestic cooking, while the remaining 74 used liquefied petroleum gas (LPG) and served as a reference population. All the individuals had comparable socioeconomic backgrounds and were between 20 and 55 years of age. Significantly higher levels of DNA damage were observed for BMF users than for LPG users. For BMF users in comparison with the reference population, Olive tail moment was 3.83 +/- 0.15 (arbitrary units) vs. 2.77 +/- 0.07 (P < 0.001); % tail DNA was 11.19 +/- 0.35 vs. 8.29 +/- 0.20 (P < 0.001); and comet tail length (microm) was 51.15 +/- 1.37 vs. 40.26 +/- 0.88 (P < 0.001). Similar significant differences were found when the groups were stratified by age and length of exposure. This study suggests that exposure to BMF smoke leads to greater levels of DNA damage than exposure to LPG combustion products.

Adult↗
PubMedDate not supplied

Investigation into possible DNA damaging effects of ultrasound in occupationally exposed medical personnel--the alkaline comet assay study.

In the present paper the possible DNA damaging effects of ultrasound in occupationally exposed medical personnel were investigated using the alkaline comet assay. The extent of DNA migration in peripheral blood leucocytes was measured. Parameters of the comet assay were studied in 30 medical workers occupationally exposed to ultrasound and in 30 corresponding unexposed control subjects. It was found that the subjects who were occupationally exposed to ultrasound for various periods of time showed a highly significant increase in levels of DNA damage compared with the control. The results obtained have confirmed the usefulness of the alkaline comet assay as a sensitive biodosimetric method, reflecting the current level of DNA damage and/or repair in peripheral blood leucocytes of ultrasound-exposed subjects. In spite of their limitations, the results of the present investigation indicate that individuals occupationally exposed to ultrasound may experience an increased genotoxic risk, emphasizing the need for more research into the nature and extent of the biological consequences to medical personnel working with ultrasonic equipment.

Adult↗
PubMedDate not supplied

Assessment of genome damage in a population of Croatian workers employed in pesticide production by chromosomal aberration analysis, micronucleus assay and Comet assay.

The widespread use of pesticides suggests that the evaluation of their genotoxicity should be extended using the different assays available. In the present study we used two standard cytogenetic methods (chromosomal aberration analysis and micronucleus assay) and the Comet assay as a relatively new and powerful technique. The study included 10 workers occupationally exposed to a complex mixture of pesticides (atrazine, alachlor, cyanazine, 2,4-dichlorophenoxyacetic acid, malathion) during their production and 20 control subjects with no history of exposure to any physical or chemical agents. For the chromosomal aberration analysis, whole blood was cultivated for 48 h, whereas for the micronucleus assay, whole blood was cultivated for 72 h. For the comet assay whole blood was embedded in agarose on a microscope slide, lysed with detergent, denaturated and subjected to alkaline electrophoresis. Damage to DNA was evaluated by measuring tail length and calculating the tail moment. A significantly increased number of chromatid and chromosome breaks, as well as the presence of dicentric chromosomes and chromatid exchanges in exposed subjects compared with control subjects (P < 0.05), was found. There was also a statistically significant difference in frequency and distribution of micronuclei between the two groups examined. In the exposed subjects the Comet assay showed a statistically significant (P < 0.001) increase in DNA migration. Results suggest that long-term occupational exposure to pesticides could cause genome damage in somatic cells and therefore may represent a potential hazard to human health.

Adult↗
PubMed2001

In vivo genotoxic effect of cadmium chloride in mice leukocytes using comet assay.

The alkaline single cell gel electrophoresis (SCGE) or "comet" assay under alkaline conditions was used to measure DNA damage in the leukocytes of Swiss Albino male mice exposed to cadmium chloride (CdCl(2)). The effect of CdCl(2) was studied after a single acute oral administration of a range of doses starting from 0.5 to 128.0 mg/kg b.wt of CdCl(2). The samples of whole blood were collected from each mouse at 24, 48, 72, and 96 h post-treatment to study single/double strand breaks in DNA. A significant increase in mean comet tail length indicating DNA damage was observed with CdCl(2) at 24 h post-treatment (P<0.05) with CdCl(2) when compared to controls. A gradual decrease in the mean tail length was observed at 48 h post-treatment indicating repair of the damaged DNA. The mean tail length showed a dose-related increase and time-dependent decrease after treatment with CdCl(2) when compared to controls. The study also confirms that the comet assay is a sensitive and rapid method to detect DNA damage caused by heavy metal like Cadmium (Cd).

Animals↗
PubMed2002

Genotoxicity of cyanobacterial extracts containing microcystins from Polish water reservoirs as determined by SOS chromotest and comet assay.

Toxicity of cyanobacterial blooms, an increasing problem around the world, is connected to the increase in bloom samples containing microcystins, caused by excessive eutrophication of drinking- and recreational water reservoirs. Microcystins are the most common group of cyanobacterial hepatotoxins. In Poland they are produced mainly by the Microcystis genus. The toxicity of microcystins has been well documented, but investigation into their genotoxicity has been insufficient relative to the study of their overall toxicity. Therefore, the aim of this study was the estimation and comparison of the genotoxicity of cyanobacterial extracts with microcystins (CEMs) using the SOS chromotest (bacterial test) with Escherichia coli PQ37 and the comet assay with human lymphocytes. Cyanobacterial bloom samples were collected in the summer months from two Polish water reservoirs, one at Sulejów and one at Jeziorsko. The SOS chromotest, which used prokaryotic cells (without metabolic activation), and the comet assay, which used eukaryotic cells, both indicated the potential genotoxic effect of CEMs. Cyanobacterial extracts caused DNA damage in human lymphocytes in vitro. The maximum level of DNA damage was observed after 12 h incubation with CEMs. The bacterial test indicated a dependence of the degree of CEM genotoxicity, the composition, and the concentration of microcystins in each bloom sample examined with the time of exposure. Differences between the genotoxicity of cyanobacterial extract and the standard microcystin-LR were noticeable. This was probably caused by the interaction of different microcystin variants. The results showed that CEMs from Polish water reservoirs were genotoxic, which was reflected by the stimulation of the SOS repair system in bacterial cells (SOS chromotest) and by the damage induced in DNA in human lymphocytes (comet assay).

Comet Assay↗
PubMed2001

Detection of DNA damage in two cell lines from rainbow trout, RTG-2 and RTL-W1, using the comet assay.

Screening methods to indicate the genotoxic potential of individual chemicals or environmental mixtures rely mainly on short-term bacterial tests. Differences in the genotoxic response of prokaryotic and eukaryotic cells necessitate the development of nonbacterial screening assays. A promising approach for this purpose could be the comet (single-cell gel electrophoresis) assay performed with fish cells in vitro. In the present study, we evaluated the comet assay with two different fish cell lines from rainbow trout (Oncorhyhnchus mykiss), the fibroblast-like RTG-2 cell line established from gonad tissue, and the epitheloid RTL-W1 cell line established from liver tissue. The cells were exposed in vitro during 2 hr to the genotoxins, 4-nitroquinoline-1-oxide (NQO), and benzo(a)pyrene (BaP), as well as to environmental samples. The LOEC values for NQO were similar in both cell lines, whereas for BaP, the RTL-W1 cells were found to be more sensitive than the RTG-2 cells. The slopes of the concentration-response curves of the two test compounds differed between the two cell lines, with RTG-2 cells showing a steeper slope for NQO, and RTL-W1 cells showing a steeper slope for BaP. When exposed to environmental samples from a remediation site, the RTL-W1 cell line, but not the RTG-2 cell line, indicated a genotoxic potential of the samples. The differences in the genotoxic response pattern of the two cell lines could be only partly explained in relation to metabolic enzymes, cytochrome P4501A, glutathione-S-transferase, and xenobiotic reductase. The findings of this study demonstrate that the comet assay with fish cell lines is suitable as in vitro screening assay in environmental genotoxicity testing, but the choice of test cell line may be critical.

Animals↗
PubMed2004

Detection and quantification of genotoxicity in wastewater-treated Tetrahymena thermophila using the comet assay.

In the present study, the comet, or single-cell, gel electrophoresis assay was adapted for use with the ubiquitous unicellular protozoan Tetrahymena thermophila, and the method was evaluated for its ability to detect DNA damage induced by known genotoxins and wastewater samples. The original comet assay protocol was substantially modified (e.g., lower concentrations of detergents were used in the lysis buffer; electrophoresis time was reduced). Using the modified method, T. thermophila were subjected to short exposures of phenol, hydrogen peroxide, and formaldehyde, leading to concentration-dependent increases in DNA damage. The genotoxic potential of influent and effluent water samples from a local municipal wastewater treatment plant was evaluated. The results indicated that the influent wastewater was genotoxic and that the genotoxicity in the effluent water was substantially reduced. We assume employing T. thermophila in the use of the comet assay may become a cost-effective and reliable tool for genotoxicity screening and monitoring of wastewater and similar systems.

Animals↗
PubMed2004

Radioprotective effects of amifostine in vitro and in vivo measured with the comet assay.

PURPOSE: The authors investigated whether a potential radioprotective effect of amifostine (WR-2721) after in vitro or in vivo administration can be detected with the comet assay. Moreover, it was determined whether radioprotection by WR-2721 is dependent on the concentration of amifostine or alkaline phosphatase (AP, the enzyme which activates the prodrug). Furthermore, the authors tried to detect possible interindividual differences in radioprotection by amifostine. MATERIAL AND METHODS: In vitro administration of amifostine: Freshly isolated lymphocytes from two healthy volunteers were incubated with different concentrations of AP (0-210 U/ml) and amifostine (0-5,000 microg/ml). IN VIVO ADMINISTRATION OF AMIFOSTINE: Blood samples were collected from six postoperative rectal cancer patients before and after intravenous administration of amifostine 500 mg (no pretreatment with radio- or chemotherapy). Leukocytes and lymphocytes were irradiated and repaired in vitro and investigated with the alkaline comet assay. The radioprotective effect was evaluated by calculating dose-modifying factors (DMFs) and the paired t-test. RESULTS: Amifostine alone did not alter the radiation-induced DNA damage in vitro. The addition of at least 0.5-1 U/ml AP was required. A significant radioprotective effect (p < 0.05) was seen after administration of amifostine in vitro for all concentrations investigated (250-5,000 microg/ml, initial DNA damage). A comparable radioprotective effect after in vivo administration of 500 mg amifostine was measured with a mean DMF of 0.87. Interindividual differences were present in vivo and in vitro. CONCLUSION: Amifostine 500 mg intravenously yields an adequate radioprotective concentration. The effect was only marginally improved by extreme concentrations of amifostine in in vitro experiments. The comet assay is capable of detecting small changes in radiosensitivity by amifostine.

Adult↗
PubMed2004

Transient increase in micronucleus frequency and DNA effects in the comet assay in two patients after intoxication with 2,3,7,8-tetrachlorodibenzo- p-dioxin.

BACKGROUND: The genotoxic effects in two patients with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) intoxication were measured; an association with the workplace was suspected. METHODS: We determined sister chromatid exchange (SCE), micronuclei (MN) and comet assay tail factor in peripheral lymphocytes of the patients and of control persons. RESULTS: A determination of polychlorinated dibenzo- p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) revealed almost pure TCDD at a concentration of 144,000 pg/g blood lipids in patient 1 and 26,000 pg/g blood lipids in patient 2, the first value being the highest level ever reported in humans. The source of TCDD ingestion remains unclear, since TCDD blood levels in 30 employees from the same workplace were in the normal range (1.2-8.6 pg/g blood lipids, average 3.0 pg/g), with the exception of three employees with moderately increased TCDD levels of 93, 149 and 856 pg/g blood lipids, who, however, did not show any clinical symptoms. Systematic measurements of air and equipment did not identify the source of TCDD. We determined SCE and MN in the peripheral lymphocytes of the patients and of control persons. A first determination, a few months after the manifestation of chloracne, showed normal values (2.4 and 2.5 MN/500 binucleated cells; 6.7 +/- 2.2 and 6.0 +/- 2.5 SCEs/metaphase) in both patients. Two months later, when TCDD levels were 85,600 pg/g blood lipids and 17,700 pg/g blood lipids, respectively, MN had increased enormously to 16 and 21.8/500 binucleated cells, SCE remained within normal range. One employee had a TCDD level of 856 pg/g blood lipids but did not develop any clinical symptoms or genotoxic effects, nor did three healthy employees with TCDD levels within background range (1.5-2.9 pg/g blood lipids). Within a period of 13 months, MN had returned to a nearly normal range in both patients. SCE had been within normal ranges all the time. We also determined the comet assay tail factor (DNA damage level) in peripheral lymphocytes of the patients. A first determination, when the TCDD level was 85,600 pg/g blood lipids (proband 1), showed an enormously high value of 33.5%. Nine months later, when the TCDD level was at 73,900 pg/g blood lipids, we found only a moderately increased value of 6.9%. Proband 2 did not have a significantly elevated comet assay tail factor, neither at the TCDD level of 17,700 pg/g blood lipids nor at the level of 15,700 pg/g blood lipids. CONCLUSIONS: This delayed and transient effect seems to indicate some kind of "indirect" or "secondary" genotoxic effect of TCDD. However, DNA damaging effects, caused directly or indirectly, could be an indicator for a possible carcinogenic risk of TCDD.

Benzofurans↗
PubMed2005

Use of comet and micronucleus assays to measure genotoxicity in meadow voles (Microtus pennsylvanicus) living in golf course ecosystems exposed to pesticides.

The purpose of this study was to conduct a biomonitoring study to measure the effects of pesticide exposure in meadow voles (Microtus pennsylvanicus) living in golf courses of the Ottawa/Gatineau region of Canada. In this article we present the results from the comet and micronucleus assay. Voles were captured in 2001 and 2002 at five golf courses and two reference sites. Blood was collected from sedated voles. Three animals from each course were euthanized to determine body burdens of historically used organochlorine (OC) and metal-based pesticides. Exposure to in-use pesticides was determined from detailed golf course pesticide use records. Comet tail length and tail moment were not related to body burdens of OC pesticides and metals historically used on these golf courses. In generally, tail length and moment significantly decreased in relation to days since last application of a pesticide, and to days since the last application of a specific fungicide (Daconil) containing a potentially genotoxic active ingredient (chlorothalonil). The slopes of these curves in 2002 were not significantly different than the half-life decay curve of chlorothalonil on vegetation. Both comet assay parameters appeared to increase in a dose-dependent manner with the amount of the last application Daconil. The number of micronucleated polychromatic erythrocytes was not related to any pesticide application parameter.

Animals↗
PubMed2005

Detection of oxaliplatin-induced DNA crosslinks in vitro and in cancer patients using the alkaline comet assay.

Oxaliplatin is frequently used in the therapy of cancer. In DNA, oxaliplatin induces, like cisplatin, the formation of crosslinks, which are commonly accepted as being responsible for the cytotoxicity of platinum agents. The detection of oxaliplatin-induced DNA crosslink formation and repair could be a good measure of assessing how a patient is responding to the agent. In this study, we used a validated modification of the alkaline comet assay for detecting the presence of these crosslinks in vitro and in cancer patients. The H460 tumour cell line was treated in vitro with a range of oxaliplatin and cisplatin doses, and the subsequent crosslink formation and repair compared between the two agents. In addition, lymphocytes from cancer patients undergoing oxaliplatin-based chemotherapy were assayed for the formation and repair of oxaliplatin-induced crosslinks. A dose-response was observed in the in vitro samples, with cisplatin producing more crosslinks than oxaliplatin at equimolar concentrations and lesions induced by both agents showing different repair efficiencies. Furthermore, evidence of crosslink formation and repair was observed in the peripheral blood lymphocytes of all cancer patients studied, along with the detection of interindividual variability in crosslink formation and repair efficiencies. To the best of our knowledge, this is the first time that oxaliplatin DNA crosslinks have been detected either in vitro or in patient samples using the alkaline comet assay. Due to its sensitivity, rapidity, small cell sample and low cost, the alkaline comet assay is a good method for the detection of oxaliplatin-induced crosslinks and their subsequent repair and, in future clinical studies, could prove to be a valuable tool in assessing/predicting a patient's response to chemotherapy.

Aged↗
PubMed2004

Lack of genotoxicity of potassium iodate in the alkaline comet assay and in the cytokinesis-block micronucleus test. Comparison to potassium bromate.

Iodine could be added to the diet of human population in the form of iodide or iodate but iodate had not been adequately tested for genotoxicity and carcinogenicity. In the present study, genotoxic effects of potassium iodate were evaluated in vitro using the alkaline comet assay and the cytokinesis-block micronucleus assay on CHO cells and compared to halogenate salt analogues potassium bromate and chlorate and also to their respective reduced forms (potassium iodide, bromide and chloride). The results showed that the comet assay failed to detect the presence of DNA damage after a treatment of cells by potassium iodate for concentrations up to 10 mM. This absence of primary DNA damage was confirmed in the cytokinesis-block micronucleus assay. In the same way, results showed that potassium chlorate as well as potassium iodide, bromide and chloride did not induced DNA damage in the alkaline comet assay for doses up to 10 mM. By contrast, potassium bromate exposure led to an increase in both DNA damage and frequency of micronucleated cells. The repair of bromate-induced DNA damage was incomplete 24 h after the end of treatment. These results seem to indicate that potassium bromate would induce DNA damage by several mechanisms besides oxidative stress.

Animals↗