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Biomedical subjects

M Laget

Publications and source records attributed to M Laget.

At least 37 records · Page 2Linked to original sources

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↗

[Assay of micronuclei in binucleated T-lymphocytes. Analysis of the distribution and variation factors in a population of 100 subjects].

The authors analysed micronuclei levels distribution in lymphocytes of 100 non occupationally exposed subjects and studied the effect of age, sex and smoking of donors on the distribution. Results showed that micronucleated cells were distributed according to a normal distribution (average = 9.5 +/- 4 micronucleated cells in 1,000 binucleated lymphocytes). Age and sex of donors had no effect on the distribution but, concerning smoking, the results showed that micronuclei levels were correlated to the number of cigarettes daily smoked.

Adult↗

Genotoxic activity of potassium permanganate in acidic solutions.

Potassium permanganate (KMnO4) combined with sulfuric acid is a strongly oxidizing mixture which has been recommended for the destruction and the decontamination of various mutagens/carcinogens in the publication series of the International Agency for Research on Cancer. Evaluation of the genotoxicity of 4 potassium permanganate solutions was performed using a microtechnique of the Ames test with the tester strains TA97, TA98, TA100 and TA102 with and without metabolic activation. Presence of direct-acting mutagens was detected in all the samples with the tester strain TA102 without S9 mix (163-357 revertants/microliters of the solutions). Three samples containing either acetone or ethanol as an organic solvent also induced a mutagenic response on tester strain TA100 without S9 mix (167-337 revertants/microliters). In addition, DNA damage in human peripheral blood lymphocytes was also measured for one of the mixtures by a new technique: the single-cell gel assay (SCGA). A sample with no organic solvent induced DNA damage in human lymphocytes with a dose-response relationship as determined by SCGA. The major mutagenic agent generated by the permanganate solutions was found to be manganese ion (Mn2+). Both manganese sulfate (MnSO4) and manganese chloride (MnCl2) gave mutagenic dose-response relationships on tester strain TA102 without S9 mix. The mutagenic potencies were 2.8 and 2.4 revertant/nmole for MnSO4 and MnCl2 respectively. MnCl2 also induced DNA damage in human lymphocytes as determined by the SCGA. The genotoxic effects of KMnO4 in acidic conditions were probably mediated by the conversion of MnO4- to Mn2+. KMnO4 in alkaline solutions did not produce mutagenic species and may offer an alternative for the degradation of genotoxic compounds.

Biotransformation↗

A high galactic latitude survey of far-ultraviolet excess objects.

Optical spectra have been obtained for a selection of objects included in a catalog of far ultraviolet bright, high galactic latitude objects detected with a balloon-borne survey telescope. The observed objects provide a sample of subdwarf O and B stars, white dwarfs, and binary systems including a hot subluminous member. Model atmospheres analysis of the subdwarf sample is used to determine the temperature, gravity, and helium to hydrogen ratio of the individual objects. A smooth distribution of objects is found on the gravity versus temperature diagram near the theoretical location of the extended horizontal branch. A break between the helium rich and helium poor objects occurs at 40,000 K. Suspected binary objects were found and analyzed to determine the temperature and gravity of the hot subluminous member in each system. The number of subdwarf stars contained in binaries is determined to be from 65% to 100%. The number versus ultraviolet magnitude distribution of the subdwarf B sample is modeled to obtain a midplane density of 3.3 10(-6) pc-3 and a population scale height of 240 pc. The proportion of white dwarfs that experience the subdwarf phase of evolution is found to be 0.94%.

Astronomy↗

Evaluation of methods for destruction of some alkylating agents.

Destruction procedures for dimethylsulfate (DMS), diethylsulfate (DES), methyl methanesulfonate (MMS), and ethyl methanesulfonate (EMS) have been investigated using treatment by 1 N NaOH, 1 N NH4OH, 1 M Na2CO3, and 1 M Na2S2O3. During the kinetic study of the destruction process, the determination of remaining concentrations of the alkylating agents was performed by the derivatization of p-nitrophenoxide to p-nitroanisole and p-nitrophenetole, which were separated by high performance liquid chromatography. The mutagenic activity of the destruction products was evaluated by the Ames test using Salmonella tester strains TA97, TA98, TA100, and TA102. The kinetics of destruction in every case followed a time-dependent exponential relationship. Solutions of 1 M Na2S2O3 showed the highest capacity for destruction of the four alkylating agents, half-lives of DMS, DES, MMS, and EMS being 0.14 min, 1.26 min, 0.60 min, and 5.26 min, respectively. No mutagenic activity was detected following complete destruction in 1 M Na2S2O3.

Alkylating Agents↗

Antimutagenic activity of some saponins isolated from Calendula officinalis L., C. arvensis L. and Hedera helix L.

Thirteen saponins were isolated and identified from Calendula officinalis, C. arvensis and Hedera helix. Mutagenic and antimutagenic activities of these products were investigated using a modified liquid incubation technique of the Salmonella/microsomal assay. The Salmonella tester strain TA98 +/- S9 mix was used. Screening of the antimutagenic activity was performed with a known promutagen: benzo-[a]pyrene (BaP) and a mutagenic urine concentrate from a smoker (SU). Antimutagenic activities were also compared with the activity of chlorophyllin. All the saponins were found to be non-toxic and non-mutagenic for doses of 400 micrograms. Chlorophyllin inhibited the mutagenic activities of BaP (1 microgram) and SU (5 microliters) in a dose-dependent manner. The four saponins from C. arvensis and the three saponins from H. helix showed antimutagenic activity against BaP (1 microgram) and SU (5 microliters) with a dose-response relationship. The possible mechanism of the antimutagenic activity of saponins is discussed.

Animals↗

Applicability of the SOS Chromotest to detect urinary mutagenicity caused by smoking.

The mutagenicity of urine obtained from five cigarette smokers was investigated using two bacterial assays: the Ames test and the SOS Chromotest. Urinary mutagens were extracted on Amberlite XAD-2 resin. Four urine samples showed activity towards Salmonella typhimurium tester strain TA98 with S9 mix while no SOS-inducing activity could be measured with Escherichia coli strain PQ37 in the SOS Chromotest. Using factorial design and a positive control benzo[a]pyrene (BaP), the concentration of S9, nicotinamide adenine dinucleotide phosphate (NADP) and glucose-6-phosphate (G6P) were optimized (2%, 0.5 mM and 10 mM respectively) for the SOS Chromotest. The SOS-inducing power of BaP was 1.42/nM with the standard S9 mix and 3.26/nM with the optimized S9 mix. B buffer and the age of L-broth were found to decrease the sensitivity of beta-galactosidase assays in the SOS Chromotest. A 4000-fold urine concentrate from a smoker was finally tested using the Ames test and the modified SOS Chromotest. Mutagenic and toxic activities were found toward tester strain TA98 (+S9 mix) showing that the SOS Chromotest is not at present suitable for assaying urinary mutagens in the presence of an in vitro metabolic activating mixture.

Adult↗

Urine mutagenicity of steel workers exposed to coke oven emissions.

Urine mutagenicity of 19 individuals was investigated at a steel mill. All the subjects worked on the coal processing unit. Urine samples were collected at the end of a working day. Urine samples of two exposed workers were collected at the end of two periods of rest and two periods of working. Mutagens were extracted on XAD-2 resin and tested by the Salmonella microsomal assay and the SOS spot test. Mutagenic potencies of exposed smokers and exposed non-smokers were 8.62 +/- 6.56 and 1.1 +/- 0.48 revertants/mg creatinine respectively with Salmonella typhimurium strain TA98 + S9. Both values were significantly higher than those of unexposed smokers and non-smokers (5.07 +/- 3.33 and 0.47 +/- 0.72 revertants/mg creatinine respectively). The urinary mutagenic potency of the two exposed individuals increased at the end of periods of working (15.97 +/- 2.57 revertants/mg creatinine) and decreased at the end of periods of rest (12.31 +/- 2.45 revertants/mg creatinine). Urinary mutagens were detected with S. typhimurium strain TA100 + S9 to a lesser extent. No direct-acting mutagens were detected by the SOS spot test. Atmospheric benzo[a]pyrene (BaP) were also measured by h.p.l.c. on the coke battery. BaP concentrations ranged between 0.01 and 0.6 microgram/m3 air at the different working sites. Biological monitoring with short-term tests is discussed.

Air Pollutants, Occupational↗

[Not Available].

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France↗