Michel Méo | Aix-Marseille University (original) (raw)
Papers by Michel Méo
Genetics and Molecular Research, 2013
Anti-Infective Agents, 2014
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
The genotoxicity of metronidazole (MZ) and dimetridazole (DZ) has been evaluated in human lymphoc... more 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.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Genetic Toxicology, 1996
The Salmonella sulA-test is a newly developed colorimetric assay to detect genotoxins. This techn... more 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.
Biotechnology Techniques, 1997
The Salmonella sulA-test using Salmonella typhimurium TA1538/pEM1968 ( sulA:: lacZ) is a new SOS-... more The Salmonella sulA-test using Salmonella typhimurium TA1538/pEM1968 ( sulA:: lacZ) is a new SOS-repair inducing system that detects mutagens and carcinogens. The b-galactosidase activity, currently detected by colorimetric dosage, can be measured by flow cytometry using a fluorescent substrate (fluorescein-di-b-D-galactopyranoside). Comparison of the dose-response relationships of eight chemicals determined by the two techniques showed that the Salmonella sulA-test combined with
American Industrial Hygiene Association Journal, 1994
Therapeutic Drug Monitoring, 1995
Archives of Andrology, 1997
The aim of this investigation was to study the pattern of luteinizing hormone (LH) secretion in m... more The aim of this investigation was to study the pattern of luteinizing hormone (LH) secretion in men with mild and moderate hypertension. LH pulsatility was evaluated for 8 h in 14 male patients, subdivided into 2 groups; group A, consisting of 8 patients, whose systolic blood pressure ranged between 180 and 160 mm Hg and whose diastolic blood pressure was between 115 and 105 mm Hg; and group B, 6 patients whose systolic blood pressure ranged between 220 and 180 mm Hg and whose diastolic blood pressure was between 104 and 95 mm Hg. Seven healthy males were evaluated as controls (group C). The major changes of LH pulsatility in group A included an increased peak width, increased peak amplitude, and increased peak area. In group B the changes followed the same pattern as in group A, but were more pronounced. The number of LH peaks was reduced, the peak width was increased, and both peak amplitude and peak area were increased as compared to the control group. The pattern of LH pulsatility is altered in essential hypertension and the main feature is represented by the prolonged duration of LH peaks and their greater amplitude. The altered pattern of LH secretion is likely to reflect a primary hypothalamic derangement with the gonadotropin releasing hormone (Gn-RH) secreting neurons remaining synchronized for longer times and secreting larger Gn-RH masses than in normal subjects. Since the nuclei of the brain stem (A1-A6) involved in the control of Gn-RH secretion respond to blood pressure changes, the altered activity of monoaminergic neurons may be the link between hypertension and changes of LH pulsatility.
Pharmaceutical Biology, 2014
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2013
Journal of Natural Products, 2010
Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. ... more Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. The mutagenicity, DNA-damaging capacities, and clastogenicity of this molecule were evaluated by the Salmonella typhimurium mutagenicity assay (Ames test) on tester strains TA97a, TA98, TA100, and TA102, the alkaline comet assay, and the micronucleus assay on CHO cells. All tests were performed with and without the metabolization mixture, S9 mix. In the Ames test, the mutagenicity of 1 was limited to TA102 without S9 mix (2.3 rev microg(-1)). The genotoxicity was more evident without S9 mix (0.78 OTMchi(2) units microg(-1) mL) than with the metabolic mixture (0.16 OTMchi(2) units microg(-1) mL) with the comet assay. Similarly, the clastogenicity without S9 mix was 0.99 MNC microg(-1) mL and 0.38 MNC microg(-1) mL with S9 mix in the micronucleus assay. The interaction of 1 with DNA is probably through the involvement of oxidative DNA lesions.
Inhalation Toxicology, 2006
In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to inte... more In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to internal contamination, with various exposure scenarios depending on the workplace. These exposures can be chronic, repeated, or acute, and can involve many different compounds. The effect of uranium after multiple scenarios of exposure is unknown. The aim of this study, therefore, was to investigate the genotoxic and biokinetics consequences of exposure to depleted insoluble uranium dioxide (UO2) by repeated or acute inhalation on subsequent acute inhalation of moderately soluble uranium peroxide (UO4) in rats. The results show that UO2 repeated preexposure by inhalation increases the genotoxic effects of UO4 inhalation, assessed by comet assay, in different cell types, when UO4 exposure alone has no effect. At the same time, the study of UO4 bioaccumulation showed that the UO4 biokinetics in the kidneys, gastrointestinal tract, and excreta, but not in the lungs, were slightly modified by previous UO2 exposures. All these results show that both genotoxic and biokinetics effects of uranium may depend on preexposure and that repeated exposure induces a potentiation effect compared with acute exposure.
Geochimica et Cosmochimica Acta, 2006
16th Annual V M Goldschmidt Conference, Melbourne, AUSTRALIA, AUG-SEP -, 2006International audien... more 16th Annual V M Goldschmidt Conference, Melbourne, AUSTRALIA, AUG-SEP -, 2006International audienceno abstrac
Food and Chemical Toxicology, 2003
European Journal of Medicinal Chemistry, 2009
The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines w... more The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.
Genetics and Molecular Research, 2013
Anti-Infective Agents, 2014
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
The genotoxicity of metronidazole (MZ) and dimetridazole (DZ) has been evaluated in human lymphoc... more 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.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1997
Mutation Research/Genetic Toxicology, 1996
The Salmonella sulA-test is a newly developed colorimetric assay to detect genotoxins. This techn... more 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.
Biotechnology Techniques, 1997
The Salmonella sulA-test using Salmonella typhimurium TA1538/pEM1968 ( sulA:: lacZ) is a new SOS-... more The Salmonella sulA-test using Salmonella typhimurium TA1538/pEM1968 ( sulA:: lacZ) is a new SOS-repair inducing system that detects mutagens and carcinogens. The b-galactosidase activity, currently detected by colorimetric dosage, can be measured by flow cytometry using a fluorescent substrate (fluorescein-di-b-D-galactopyranoside). Comparison of the dose-response relationships of eight chemicals determined by the two techniques showed that the Salmonella sulA-test combined with
American Industrial Hygiene Association Journal, 1994
Therapeutic Drug Monitoring, 1995
Archives of Andrology, 1997
The aim of this investigation was to study the pattern of luteinizing hormone (LH) secretion in m... more The aim of this investigation was to study the pattern of luteinizing hormone (LH) secretion in men with mild and moderate hypertension. LH pulsatility was evaluated for 8 h in 14 male patients, subdivided into 2 groups; group A, consisting of 8 patients, whose systolic blood pressure ranged between 180 and 160 mm Hg and whose diastolic blood pressure was between 115 and 105 mm Hg; and group B, 6 patients whose systolic blood pressure ranged between 220 and 180 mm Hg and whose diastolic blood pressure was between 104 and 95 mm Hg. Seven healthy males were evaluated as controls (group C). The major changes of LH pulsatility in group A included an increased peak width, increased peak amplitude, and increased peak area. In group B the changes followed the same pattern as in group A, but were more pronounced. The number of LH peaks was reduced, the peak width was increased, and both peak amplitude and peak area were increased as compared to the control group. The pattern of LH pulsatility is altered in essential hypertension and the main feature is represented by the prolonged duration of LH peaks and their greater amplitude. The altered pattern of LH secretion is likely to reflect a primary hypothalamic derangement with the gonadotropin releasing hormone (Gn-RH) secreting neurons remaining synchronized for longer times and secreting larger Gn-RH masses than in normal subjects. Since the nuclei of the brain stem (A1-A6) involved in the control of Gn-RH secretion respond to blood pressure changes, the altered activity of monoaminergic neurons may be the link between hypertension and changes of LH pulsatility.
Pharmaceutical Biology, 2014
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2013
Journal of Natural Products, 2010
Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. ... more Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria kotschyi roots. The mutagenicity, DNA-damaging capacities, and clastogenicity of this molecule were evaluated by the Salmonella typhimurium mutagenicity assay (Ames test) on tester strains TA97a, TA98, TA100, and TA102, the alkaline comet assay, and the micronucleus assay on CHO cells. All tests were performed with and without the metabolization mixture, S9 mix. In the Ames test, the mutagenicity of 1 was limited to TA102 without S9 mix (2.3 rev microg(-1)). The genotoxicity was more evident without S9 mix (0.78 OTMchi(2) units microg(-1) mL) than with the metabolic mixture (0.16 OTMchi(2) units microg(-1) mL) with the comet assay. Similarly, the clastogenicity without S9 mix was 0.99 MNC microg(-1) mL and 0.38 MNC microg(-1) mL with S9 mix in the micronucleus assay. The interaction of 1 with DNA is probably through the involvement of oxidative DNA lesions.
Inhalation Toxicology, 2006
In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to inte... more In nuclear fuel cycle facilities, workers may inhale airborne uranium compounds that lead to internal contamination, with various exposure scenarios depending on the workplace. These exposures can be chronic, repeated, or acute, and can involve many different compounds. The effect of uranium after multiple scenarios of exposure is unknown. The aim of this study, therefore, was to investigate the genotoxic and biokinetics consequences of exposure to depleted insoluble uranium dioxide (UO2) by repeated or acute inhalation on subsequent acute inhalation of moderately soluble uranium peroxide (UO4) in rats. The results show that UO2 repeated preexposure by inhalation increases the genotoxic effects of UO4 inhalation, assessed by comet assay, in different cell types, when UO4 exposure alone has no effect. At the same time, the study of UO4 bioaccumulation showed that the UO4 biokinetics in the kidneys, gastrointestinal tract, and excreta, but not in the lungs, were slightly modified by previous UO2 exposures. All these results show that both genotoxic and biokinetics effects of uranium may depend on preexposure and that repeated exposure induces a potentiation effect compared with acute exposure.
Geochimica et Cosmochimica Acta, 2006
16th Annual V M Goldschmidt Conference, Melbourne, AUSTRALIA, AUG-SEP -, 2006International audien... more 16th Annual V M Goldschmidt Conference, Melbourne, AUSTRALIA, AUG-SEP -, 2006International audienceno abstrac
Food and Chemical Toxicology, 2003
European Journal of Medicinal Chemistry, 2009
The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines w... more The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.