Biomedical subjects

M Laget

Publications and source records attributed to M Laget.

At least 19 recordsLinked to original sources

PubMed2002

Synergistic in vitro antimalarial activity of plant extracts used as traditional herbal remedies in Mali.

In Mali, where malaria is endemic, plants are extensively used for treating periodic fevers and malaria. According to the advice of traditional medicine, plants are often mixed during the preparation of febrifugal decoctions. In previous studies, we demonstrated the potent in vitro antimalarial activity of extracts isolated from four plants commonly used in traditional remedies: Mitragyna inermis (Willd.) O. Kuntze, Rubiaceae, Nauclea latifolia (Sm.), Rubiaceae, Guiera senegalensis (Gmel.), Combretaceae, and Feretia apodanthera (Del.), Rubiaceae. In the present work, we evaluate the potent in vitro synergistic antimalarial interaction between these extracts, using standard isobologram analysis. Then, we evaluate their cytotoxicity on human monocytes and their mutagenic activity on an in vitro system of two beta-carboline alkaloids isolated from Guiera senegalensis (harman and tetrahydroharman). Three combinations demonstrate a strong, synergistic, inhibitory effect on in vitro plasmodial development and are devoid of cytotoxicity towards human cells. These results justify their use in association in traditional medicine. Moreover, tetrahydroharman, isolated from G. senegalensis, presents interesting antimalarial activity, no cytotoxicity and is not genotoxic in the Salmonella Ames test with and without metabolic activation.

Animals↗

PubMed2001

Evaluation of sunscreen protection in human melanocytes exposed to UVA or UVB irradiation using the alkaline comet assay.

The in vivo assessment of sunscreen protection does not include the photogenotoxicity of UVA or UVB solar radiation. Using the comet assay we have developed a simple and rapid technique to quantify sunscreen efficacy against DNA damage induced by UV light. Cutaneous human melanocytes from primary cultures were embedded in low-melting point (LPM) agarose and exposed to UVA (0.8 J/cm2) or to UVB (0.06 J/cm2) through a quartz slide covered with 10 microL volumes of sunscreens. DNA single-strand breaks induced directly by UVA at 4 degrees C and indirectly through nucleotide excision repair by UVB following a 35 min incubation period at 37 degrees C were quantified using the comet assay. Tail moments (TM) (tail length x %tail DNA) of 100 cells/sample were determined by image analysis. DNA damage was evaluated with a nonlinear regression analysis on the normalized distribution frequencies of TM using a chi 2 function. The coefficients of genomic protection (CGP) were defined as the percentage of inhibition of DNA lesions caused by the sunscreens. Twenty-one sunscreens were evaluated, and the calculated CGP were compared with the in vivo sun protective factor (SPF) and with the protection factor UVA (PFA). Nonlinear relationships were found between SPF and CGPUVB and between PFA and CGPUVA.

Cells, Cultured↗

PubMed2000

Toxicity and genotoxicity of antimalarial alkaloid rich extracts derived from Mitragyna inermis O. Kuntze and Nauclea latifolia.

The toxicity and the genotoxicity of antimalarial alkaloid rich extracts derived from two plants used in traditional medicine in Mali (Mitragyna inermis (Willd.) O. Kuntze Rubiaceae and Nauclea latifolia (Sm.) Rubiaceae) were evaluated on in vitro and in vivo systems. The results demonstrated that an alkaloid rich extract derived from M. inermis induced a strong inhibition of protein synthesis in mammalian cells but did not exhibit mutagenic or genotoxic activity. An alkaloid rich extract derived from N. latifolia could interact in vitro with DNA of bacteria and mammalian cells, leading to G2-M cell cycle arrest and heritable DNA-damage, as well as inducing in vivo single-strand breaks in liver, kidney and blood cells.

Alkaloids↗

PubMed1999

The protective activity of alpha-hederine against H2O2 genotoxicity in HepG2 cells by alkaline comet assay.

This study was designed to evaluate the protective effect of alpha-hederine (alpha-hed) against H2O2-mediated DNA damage on HepG2 cell line by the alkaline comet assay. For the protective effect of alpha-hed study, cells were treated according to three protocols: pre-treatment, simultaneous treatment and post-treatment. The effect of alpha-hed on catalase activity was evaluated after treating the cells with 3.36 mg/ml of 3-amino-1,2,4-triazole (AMT) singly or in combination with alpha-hed (1.5 or 3 microg/ml) and H2O2 (8.8 microM) during 1 h. The catalase activity was also biochemically measured after treating cells with alpha-hed at 1.5, 3, or 15 microg/ml during 1 h. Additionally, the influence of alpha-hed on membrane RedOx potential, pool of reduced glutathione and total protein content was evaluated by flow cytometry. In the pre-treatment, the two concentrations of alpha-hed (1.5 and 3 microg/ml) decreased the lesions induced by H2O2 (8.8 microM) significantly. This decrease was about 57.2% and 66.1%, respectively. Similar results were observed when cells were treated with alpha-hed and H2O2 simultaneously. The decrease of H2O2-induced lesions was about 78.2% and 83.2% (alpha-hed 1.5 and 3 microg/ml, respectively). In the post-treatment protocol, this decrease was not significant. The combination of AMT and H2O2 induced more DNA damage than H2O2 alone (tail moment (TM) means was 31.4% and 21.8%, respectively). When alpha-hed was added to this mixture, TM means were reduced significantly (17.4% for alpha-hed 1. 5 microg/ml and 15.5% for alpha-hed 3 microg/ml). Up to 6.9 microg/ml, alpha-hed enhanced catalase activity (60.5%), followed by a decrease of the activity. Total protein content and membrane RedOx potential were slightly increased up to 11 microg/ml (14% and 3.6%, respectively) followed by a drop and a plateau. Pool of reduced glutathione remained unchanged up to 10 microg/ml then dropped and reached a plateau. In conclusion, alpha-hed could exert its protective effect against H2O2-mediated DNA damage by scavenging free radicals or by enhancing the catalase activity.

Catalase↗

PubMed1998

Evaluation of the mutagenicity and antimutagenicity of forty-two 3-substituted flavones in the Ames test.

The mutagenic and antimutagenic activities of forty-two synthetic flavones were assessed by the Ames test. The tested flavones included twenty-three 3-nitroflavones, eighteen 3-aminoflavones and the 3-chloroflavone. The mutagenicity was evaluated with Salmonella typhimurium TA100 and YG1042 (an overproducing nitroreductase and O-acetyltransferase TA100 strain) with and without metabolic activation (S9 mix). The antimutagenicity of the non mutagenic derivatives was evaluated against 11 known reference mutagens. A total of 39 synthetic flavones were mutagenic. The mutagenic activities ranged from 0.1 rev/nmole (4'-chloro-6-methoxy-3-nitroflavone) to 6240 rev/nmole (4'-methoxy-3, 3'-diaminoflavone). Two differences were found between the 3-amino and the 3-nitroflavones: (i) the mutagenicity of the 3-aminoflavones required the presence of the metabolic activation; (ii) the 3-amino derivatives were more mutagenic than their 3-nitro counterparts. Increased mutagenicity, as assessed with strain YG1042, was limited to 17/39 derivatives. The mutagenic activity was induced by the presence of the double bond at the 2,3-position for conjugation of the lone-pair electron with the carbonyl group on the 'C' ring. This mutagenicity was modulated by substituents at the 2'-position. Additional mutagenicity was brought by the aminoaromatic and nitroaromatic group reduction by bacterial nitroreductases and by the S9 mix; it was modulated by different substituents on the aromatic rings of the flavones. Three flavones: 3-chloroflavone (1C), 4'-hydroxy-3-nitroflavone (23N) and 2',3-diaminoflavone (2A) showed antimutagenic properties. Compound 1C was efficient against benzo(a)pyrene (BaP), 2-aminofluorene (2AF), 2-aminoanthracene (2AA), 4-nitroquinoline-1-oxide (4NQO) and 1-methyl-3'-nitro-1-nitrosoguanidine (MNNG). Compound 23N inhibited the mutagenicity of BaP and MNNG. The antimutagenic activity of 2A was limited to MNNG.

Antimutagenic Agents↗

PubMed1998

Chemical degradation of wastes of antineoplastic agents amsacrine, azathioprine, asparaginase and thiotepa.

As a part of a program devoted to the destruction of antineoplastic agents, three chemical methods readily available in the hospital environment, viz. oxidation with sodium hypochlorite (NaClO, 5%), hydrogen peroxide (H2O2, 30%), and Fenton reagent (FeCl2.2H2O; 0.3 g in 10 ml H2O2, 30%), were tested for the degradation of four anticancer drugs: Amsacrine, Azathioprine, Asparaginase and Thiotepa. The efficiency of the degradation was monitored by high-performance liquid chromatography. The mutagenicity of the degradation residues were tested by Ames test using tester strains Salmonella typhimurium TA 97a, TA 98, TA 100 and TA 102 with and without an exogenous metabolic activation system. Using sodium hypochlorite, 98.5% of Amsacrine, 99.0% of Azathioprine, 99.5% of Asparaginase and 98.7% of Thiotepa were destroyed after 1 hr. The hydrogen peroxide treatment destroyed 99% of Asparaginase and 98.7% of Thiotepa in 1 hr. However, this procedure was not efficient for the treatment of Amsacrine (28% after 16 hr) and of Azathioprine (53% degradation in 4 hr). The action of Fenton reagent resulted in the destruction of 98% of Amsacrine, and 99.5% of Azathioprine, 98.5% of Asparaginase and 98.7% of Thiotepa in 1 hr. In all cases where a high degree of degradation was achieved, the residues obtained weee non mutagenic.

Amsacrine↗

PubMed1997

Evaluation of the genotoxic activity of metronidazole and dimetridazole in human lymphocytes by the comet assay.

The genotoxicity of metronidazole (MZ) and dimetridazole (DZ) has been evaluated in human lymphocytes using the comet assay. The test has been performed using 3 doses (58.4, 175.2 and 292.1 microM for MZ; and 70.9, 212.6 and 354.3 microM for DZ) under 3 experimental protocols: aerobiosis, anaerobiosis (90% N2, 10% CO2) and with the presence of the microsomal fraction S9 mix. The effects of 4 antioxidants (8-hydroxyquinoline (8HQ), vitamin C (VitC), catalase (CAT) and superoxide dismutase (SOD), have been investigated on DNA damage generated by fixed concentrations of MZ (292.1 microM) and DZ (354.4 microM). In aerobic conditions, MZ and DZ produced significant dose-response relationships. The dose-related effects of both drugs decreased or were abolished in anaerobic conditions or in presence of S9 mix. 8HQ, VitC, CAT and SOD induced dose-related protective responses against DNA damage due to MZ and DZ. These findings suggest that MZ and DZ induce DNA damage in human lymphocytes through the futile cycle. The one-electron reduction of the drugs leads to the production of nitro radical anions. In the presence of oxygen, these radicals are reoxidized and generate oxygen-activated species.

Animals↗

PubMed1997

Chemical degradation of wastes of antineoplastic agents: cyclophosphamide, ifosfamide and melphalan.

Handling genotoxic compounds commonly used in cancer chemotherapy generates contaminated wastes that require decontamination before disposal. Chemical methods are an alternative and/or a complement to incineration for the treatment of wastes and spills. As part of a program initiated by the International Agency for Research on Cancer (IARC), three chemical methods readily available in the hospital environment, viz sodium hypochlorite (NaOCl, 5.25%), hydrogen peroxide (H2O2, < or = 30%) and Fenton reagent (FeCl2, 2H2O; 0.3 g in 10 ml H2O2, 30%), were tested for the degradation of three alkylating agents (cyclophosphamide, CP; ifosfamide, IF, and melphalan). Pharmaceutical preparations corresponding to the most highly concentrated administration solutions in either NaCl (0.9%) or dextrose (5%) were inactivated by oxidation volume/volume with each of the methods for at least 1 h. The efficiency of degradation was monitored by high-pressure liquid chromatography. The mutagenicity of the degradation residues was tested by means of the Ames test using tester strains of Salmonella typhimurium TA 97a, TA 98, TA 100 and TA 102 with and without an exogenous metabolic activation system. Complete disappearance of CP was observed after 1 h with all degradation methods. However, direct mutagens were generated by the Fenton oxidation technique in the presence of dextrose (5%). IF was completely degraded by the Fenton reagent and NaOCl methods. No mutagenic residues were detected after 1 h of treatment with the Fenton technique, and after 3 h with the NaOCl method. Direct-acting mutagens remained after the H2O2 treatment in the presence of dextrose (5%). Complete degradation of melphalan was achieved in 1 h by each of the three methods, and no mutagenic residues were produced by any of the treatments. The use of NaOCl (5.25%) proved the most efficient system for degradation of the three alkylating agents.

Animals↗

PubMed1997

Chemical degradation of wastes of antineoplastic agents. 2: Six anthracyclines: idarubicin, doxorubicin, epirubicin, pirarubicin, aclarubicin, and daunorubicin.

OBJECT: Handling of genotoxic compounds commonly used in cancer chemotherapy generates contaminated wastes that require decontamination before disposal. Chemical methods are an alternative and/or a complement to incineration for the treatment of wastes and spills. METHODS: As part of a program initiated by the International Agency for Research on Cancer (IARC), 3 chemical methods readily available in the hospital environment--sodium hypochlorite (NaOCl, 5.25%), hydrogen peroxide (H2O2, < or = 30%) and Fenton reagent (FeCl2, 2H2O; 0.3 g in 10 ml H2O2, 30%)--are being tested for the degradation of a total of 32 antineoplastic agents. The efficiency of degradation was monitored by high-pressure liquid chromatography. The mutagenicity of the degradation residues were tested by the Ames test using tester strains Salmonella typhimurium TA 97a, TA 98, TA 100, and TA 102 with and without an exogenous metabolic activation system. RESULTS: The first results obtained for the degradation of cyclophosphamide, ifosfamide, and melphalan have been published in this journal. The present manuscript reports the results of the investigation of a series of six anthracyclines (aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, and pirarubicin) commonly used in chemotherapy treatment. Pharmaceutical preparations corresponding to the most concentrated administration solutions in either NaCl (0.9%) or dextrose (5%) were inactivated by oxidation volume/volume with each of the methods for at least 1 h. Complete degradation into nonmutagenic residues of all the tested compounds was observed after 1 h for the NaOCl (5.25%) treatment as previously reported for the first study. CONCLUSION: Sodium hypochlorite (5.25%) is an efficient reagent for the chemical degradation of the nine drugs tested thus far.

Animals↗

PubMed1996

In vitro studies of the genotoxic effects of bitumen and coal-tar fume condensates: comparison of data obtained by mutagenicity testing and DNA adduct analysis by 32P-postlabelling.

Bitumens contain traces of polycyclic aromatic compounds (PACs), a part of which will end up in the fumes emitted during hot handling of bitumen-containing products, e.g. during roadpaving. Although exposure of workers to these fumes is low, it might lead to health problems. Studies on bitumen fume condensates (BFCs) showed weak to moderate mutagenic activities, but studies on DNA adduct formation have not been reported. Therefore, a study was initiated in which fumes were generated from two road grade bitumens, in such a way that they were representative of the fumes produced in the field. The combined vapour/particulates were tested in vitro for their ability to produce DNA adducts and in modified Ames mutation assays, using a number of different strains. An attempt was made to relate the results to chemical data, such as the content of a number of individual polycyclic aromatic hydrocarbons (PAHs) and with a measure for the total PAC content. As a reference material fume condensate from coal-tar (coal-tar pitch volatiles; CTPV) were subjected to the same tests. All fume condensates tested were mutagenic to all strains and induced the formation of DNA adducts. The patterns of DNA adducts, obtained by 32P-postlabelling, arising from the BFCs were qualitatively different from the patterns of adducts obtained from the CTPVs, implying qualitative differences in the nature of the compounds responsible for the formation of these adducts. This is corroborated by the observation that for BFCs quantitative adduct levels are higher than would be expected based on the PAH content. These data thus indicate that the PAHs analysed are not the sole components responsible for adduct formation from BFCs, but that an important contribution comes from other (hetero- and/or substituted-) PACs.

Animals↗

PubMed1996

The Salmonella sulA-test: a new in vitro system to detect genotoxins.

The Salmonella sulA-test is a newly developed colorimetric assay to detect genotoxins. This technique is based on the ability of DNA-damaging agents to induce the sulA gene, one of the SOS response genes. A constructed plasmid, pEM1968, carrying a fused sulA'::'lacZ was introduced into Salmonella typhimurium TA1538. Monitoring sulA gene expression was performed by assaying the beta-galactosidase activity in the transformed strain S. typhimurium TA1538/pEM1968. A simple, fast and sensitive liquid incubation procedure has been developed after optimization of the S9 mix composition and beta-galactosidase assay. The SOS-inducing potency (SOSIP, microM-1) was defined as the slopes of the non-linear dose-response relationships. Twenty-one chemicals with different modes of action were examined for a preliminary evaluation of the test. Nineteen chemicals were genotoxic in the Salmonella sulA-test. The SOSIP ranged from 1.2 x 10(-4) microM-1 (ethyl methanesulfonate) to 419.9 microM-1 (bleomycin). Sodium azide and 5-fluorouracil were not genotoxic. Frameshift, base-pair and oxidative genotoxins were detected by the tester strain. The calculated SOSIP and the minimum concentrations detected (MCD) in the Salmonella sulA-test were compared to the reported values obtained with two similar assays: the SOS Chromotest and umu-test. The SOSIP values of 12 compounds were the highest in this new assay. Five chemicals tested in the Salmonella sulA-test gave similar SOSIP values with those of one of the two other tests. ICR-191 had the highest SOSIP with the SOS Chromotest and 3-methylchloranthrene showed the highest SOSIP with the umu-test. Similarly, the lowest MCD values were found for 12 compounds in the Salmonella sulA-test. Four compounds had close MCD values in this assay and one of the two other techniques. The SOS Chromotest remained the most sensitive assay for cisplatin and ICR 191. The umu-test was the technique of choice for 3-methylchloranthrene.

Bacterial Proteins↗

PubMed1996

Optimization of the Salmonella/mammalian microsome assay for urine mutagenesis by experimental designs.

Assessing urine mutagenicity with the Salmonella mutagenicity test is often limited by the volumes of the samples. Optimization of the assay was performed with factorial and Doehlert designs. Two fractional factorial designs 2(3-1) (3 factors, 4 experiments) were used to estimate the main effects of the percent S9 in the mix, the time of liquid incubation, the inoculum size and the growth conditions. A Doehlert design (3 factors, 13 experiments) was used to study the main effects and the interactions of the NADP, G6P and S9 in the mix. The positive markers were benzo[a]pyrene (BaP, 0.3 microgram/plate) and a pool of smokers' urine (SU, 1.25 ml equivalent/plate). The response was limited to the induction factor (IF, number of induced revertants/number of spontaneous revertants) with Salmonella typhimurium TA98. The optimal conditions for BaP were: a 60 min period of liquid incubation and a volume of 0.1 ml (approx. 10(8) cells/plate) of an overnight culture grown in 50 ml of Nutrient Broth No. 2 from a 250 ml flask. The S9 mix (0.1 ml, final volume) included 1.5% of S9, 1.0 mM NADP and 4.4 mM G6P. The maximal IF was 15.79. The optimal conditions for SU were: a 60 min period of liquid incubation and a volume of 0.1 ml (approx. 10(8) cells/plate) of an overnight culture grown in 7 ml of Nutrient Broth No. 2 from a 20 x 180 mm tube. The S9 mix (0.1 ml, final volume) included: 4% S9, 4.2 mM NADP and 5.2 mM G6P. The maximal IF was 10.95. These optimal conditions did not modify the spontaneous frequencies of the tester strains: TA97a, TA98, TA100 and TA102. The dose-response curves of mutagenic urine samples were found to be non-linear. This micromethod required 8-fold less urine sample and 12.5-fold less liver homogenate as compared to the standard plate incorporation assay and was from 6.2- to 11.8-fold more sensitive to evaluate urine mutagenicity. The sensitivity of this technique was found to be limited to individuals smoking more than approx. 5 cigarettes/day by the standard extraction-concentration procedure.

Dose-Response Relationship, Drug↗

PubMed1995

Monitoring exposure of hospital personnel handling cytostatic drugs and contaminated materials.

A study was undertaken to evaluate the urine mutagenicity of 63 individuals working in four hospital departments. The exposed group included 38 subjects who were exposed to various cytostatic drugs and/or contaminated material from treated patients. The control group included 25 individuals of the hospital personnel. Urine mutagenicity was monitored by the Ames test using tester strains TA 98 + S9 Mix and TA 102-S9 Mix. Urine samples were collected before and after the working periods. A total of 29/116 (25%) urine samples were mutagenic for either strain. Among the mutagenic samples, 24/29 were mutagenic for tester strain TA 98 exclusively. No significant correlation could be found between occupational exposure to cytostatic drugs and urine mutagenicity evaluated by the strain TA 98 + S9 Mix. Smoking was the main environmental factor that modulated urine mutagenicity with TA 98. Three subjects in the exposed group had mutagenic urine samples at the end of the working period with strain TA 102-S9 Mix. This mutagenicity was related to occupational exposure to cisplatin. In the control group, one individual had mutagenic samples before and after the working period. Assessing occupational exposure to cytostatic drugs with strain TA 102 requires additional studies to determine environmental mutagens which can be detected by this strain.

Adult↗

PubMed1995

The micronucleus assay in human exfoliated urothelial cells: effect of smoking.

Micronucleated cell rates were examined in exfoliated urothelial cells of 73 healthy donors not occupationally exposed to mutagens or aneugens. Micronucleated cell levels averaged 0.54 +/- 0.68% in the entire population: they reached 1.09% in smokers, 0.95% in ex-smokers and 0.24% in non-smokers. Among variation factors evaluated during this study, only smoking had a significant effect on micronucleated cell rates (P = 0.007) whereas age and sex had no effect (P = 0.101 and P = 0.918). No significant difference was observed between micronucleated cell rates of smokers and ex-smokers, suggesting that smoking could generate clones of basal micronucleated cells in urothelial tissues.

Adolescent↗

PubMed1995

[A new mode of expression for the assessment of capacities of DNA repair by flow cytometry].

Flow cytometry technic was used to study DNA synthesis of Hep G2 cells following mitomycin C and adriblastine treatments during 24 hours. DNA synthesis was expressed by 2 methods: the new expression global DNA synthesis (S+G2)/G1 that considered the cells during scheduled and unscheduled DNA syntheses of S and G2 phases and the cell cycle (Fox program) that evaluated the cells during scheduled DNA synthesis by the terms G1 = 2n, S = 2n+x and G2 = 4n which excluded unscheduled DNA synthesis. The experimental data treated with this new expression led to the determination of threshold concentrations for the two tested compounds where the DNA repair mechanisms were overloaded, leading to cell death. This term was shown to be more accurate to describe the genotoxic action of compounds. Furthermore, these threshold concentrations of DNA damages was found to be linked with significant increase of micronuclei in the micronucleus test.

Antibiotics, Antineoplastic↗

PubMed1994

Potassium permanganate can be used for degrading hazardous compounds.

Solutions of potassium permanganate in 3 M sulfuric acid, 1 M sodium hydroxide solution, and water can be used to degrade hazardous compounds. Excess oxidant can be removed by using sodium metabisulfite. Manganese, a carcinogen and mutagen, can be removed from the final reaction mixtures by making these mixtures strongly basic. Aqueous dilution causes the soluble potassium sulfate to dissolve while still allowing the insoluble manganese compounds to be removed by filtration and so reduces the weight of precipitate. In all cases the amount of manganese left in the filtrates was less than 2 ppm and the reaction mixtures were nonmutagenic. When ethanol was used as a test compound, degradation was much more rapid when the solvent was 3 M sulfuric acid or 1 M sodium hydroxide solution than when the solvent was water. However, the variation of the rate of reaction with pH depends on the nature of the substrate. Thus the effectiveness of the various methods may vary for other substrates. Potassium permanganate in sulfuric acid was used to degrade four polycyclic heterocyclic hydrocarbons. Destruction was greater than 99.9% and the final reaction mixtures contained no more than 0.5 ppm manganese and were not mutagenic. By modifying the work-up procedures to remove manganese from the final reaction mixture, procedures previously developed for degrading hazardous compounds can still be employed.

Chemical Phenomena↗

PubMed1994

The micronucleus assay in human lymphocytes: screening for inter-individual variability and application to biomonitoring.

Micronuclei levels were assessed in cytokinesis-blocked lymphocytes of 200 male and female healthy donors not occupationally exposed to genotoxic risks and of 33 male industrial painters handling genotoxic substances. Frequency of micronucleated cells was 9.87 +/- 3.1 per 1000 in the control population and was shown to have a large inter-individual variability. The study of factors contributing to this variability showed that only smoking could affect micronucleated cell rate, inducing an increase of 25%, whereas age and sex had no effect. Among the industrial painters, frequency of micronucleated cells averaged 18.30 +/- 7.39 per 1000: the difference between the two populations studied was shown to be statistically significant by the Mann-Whitney rank sum test (one-sided U test) and indicated that exposed painters need preventive measures.

Adult↗

PubMed1992

Evaluation of the mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives by the Ames test and the SOS chromotest.

The mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives have been evaluated by using modified versions of the Ames test and the SOS Chromotest. Salmonella typhimurium tester strain TA 100 was used with and without metabolic activation in the Ames test and Escherichia coli tester Strain PQ 37 was used with and without metabolic activation in the SOS Chromotest. Including metronidazole and dimetridazole, 45 derivatives were mutagenic and genotoxic. The mutagenic potencies (MP) ranged from 0.127 to 53,717 revertants/nmol while the SOS induction powers (SOSIP) ranged from 0.00131 to 107 IF/nmol. The overall correlation between MP and SOSIP was r = 0.845 (n = 84) as calculated by linear regression analysis. A higher correlation was observed between MP and SOSIP without the S9 mix than with it. Among the imidazole derivatives, the 5-nitroimidazoles with a lactam ring at the 2-position showed the highest MP and SOSIP. The presence of a nitro group at the 5-position was critical for the mutagenicity and the genotoxicity of the derivatives. Substituents at the 1- and 2-positions were also found to modulate these activities.

Animals↗