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A Botta

Publications and source records attributed to A Botta.

72 records · Page 4Linked to original sources

Handling of cytostatic drugs and urine mutagenesis.

As part of a French national epidemiologic study on human reproduction among hospital personnel, we investigated urine mutagenicity of nurses and personnel from oncology units exposed to cytostatic drugs. During a first series of experiments, urine mutagenicity of 47 subjects working in six oncology units was investigated in the Marseille regional's hospital. A control group of 37 individuals working in one cardiology clinic was also included. Urinary mutagens were extracted on XAD-2 resin and tested by two bacterial mutagenicity tests: the Ames test with tester strains Salmonella typhimurium TA 97, TA 98, TA 100 and TA 102 with or without metabolic activation (S9 MiX) and the SOS Chromotest with tester strain Escherichia coli PQ 37-S9 MIX. Bactericidal activity towards the tester strains was found in 40% of the urine samples (36/90). During a second series of experiments, urine mutagenicity of 17 office clerks was also investigated. Toxicity was found in six of the 21 urine samples. No significant difference of toxicity distribution and no relationship between toxicity and cigarette smoking were found. Qualitative analysis of the data showed no significant difference among the exposed groups and the control group (Chi 2 = 0.529, df = 2) with tester strain TA 98 + S9 MIX. Cigarette smoking was found to be the main factor of increased urinary mutagenicity (Chi 2 = 0.529, df = 1). Quantitative analysis of the data showed that mutagenic potencies varied from 0.332 +/- 0.539 revertants/mg creatinine to 7.226 +/- 6.743 revertants/mg creatinine with TA 98 + S9 MIX.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

A chronobiological study of delta-amino levulinic acid urinary excretion.

Determination of urinary delta-amino levulinic acid (ALA) is now systematically used in occupational health to detect an excessive exposure to lead in professionally exposed workers. However, to determine whether circadian changes of the urinary excretion of ALA alter the significance of the test, we quantified the ALA levels in the urine of 19 healthy young adults. Urine samples were taken every 3 hr between 0700 and 2300 hr and ALA levels were determined by a spectrocolorimetric method. The data indicated that the 24-hr mean ALA level was: 1.81 mg/g creatinine. The peak values (2.24 +/- 0.24) were obtained between 1400 and 1700 hr whereas the lowest ALA levels were found between 2200 and 0300 hr. Cosinor analysis revealed a significant circadian rhythm while no significant difference could be found according to sex. Possible explanations of our findings are discussed.

Adult↗

[Frequency of microalbuminuria in an adult population].

Urinary samples overnight collected from the thousand normotensive adults with normal urinalysis and normal serum levels of creatinine, urea and glucose were tested for the presence of microalbuminuria by latex test Sclavo. Fourty-five cases were positive: the values of microalbuminuria in 21 of these cases tested with RIA method exceeded 26 mg/l; one hundred twenty-six latex-negative cases evidenced lower RIA values. The high sensitivity of the test and its clinical significance suggest the need of an automatic procedure for detecting microalbuminuria in Albustix-negative urine samples.

Adult↗

[Frequency of microalbuminuria in children].

Urinary samples overnight collected from 550 pediatric patients with normal urine analysis and normal serum levels of creatinine, urea and glucose were tested for the presence of microalbuminuria by a latex test. Only 3 cases (0.6%) were positive even with RIA method; the difference with the percentage observed in adults (4.5%) is highly significant.

Albuminuria↗

Pharmacokinetic study of ethanol after oral administration: a new approach to enzymatic elimination.

A new approach to the enzymatic elimination of ethanol in vivo allows us by means of a one-compartment model to take into account all the phases of the ethanol concentration-time curve after oral administration. The Michaelis-Menten equation is an approximation of this model; indeed it constituted the only non-linear approach to the kinetic study of ethanol. To express the model in the form of an equation leads to a third-order system of bilinear differential equations which has no analytical solution. The identification of the model is based on the optimization of a conformity criterion between experimental values and those predicted by the model. Optimization is performed by means of an iterative algorithm minimizing non-linear functions. This method permits the estimation of initial concentrations of products involved in the enzymatic reaction (substrate, enzyme) and kinetic constants (characterizing absorption and enzymatic reaction). Kinetics in nonalcoholics, alcoholics, and former alcoholics were identified using this new model. A good fit between the experimental values and the simulated curve was obtained. The in vivo estimation of the kinetic constants of each elementary step of the enzymatic reaction represents an original approach likely to provide more knowledge of ethanol metabolism.

Adult↗

[Method of plasma acetate determination by gas chromatography after ethanol administration in man (author's transl)].

Plasma acetate is extracted using ethanol in alkaline medium, in presence of internal standard. After concentration of the hydroalcoholic phase, the chromatographic analysis is performed utilizing 10% SP 1200 and 1% H3PO4 on chromosorb W. The linearity of the method has been tested from 0.05 to 10 mM/I, its reproducibility is +/- 3.5% for levels ranging from 0.1 to 10 mM/I and +/- 10% for those smaller than 0.1 mM/I. This method is sensitive enough to assess the physiological acetate levels and those obtained after ethanol biotransformation.

Acetates↗

[Approach to ethanol metabolism in man by studying the concentration-time curves of ethanol, free enzyme and plasma acetate (author's transl)].

The use of a pharmacokinetic model characterized by a new theoretical approach of the enzymatic reaction allows to account for ethanol concentration-time curve (after oral administration in man) and to simulate the evolution of free enzyme concentration. The interpretation of the various phases observed during these kinetics (ethanol, free enzyme) and plasma acetate kinetics (performed in the same study) constitutes an original approach to ethanol metabolism.

Acetates↗

[Studies on the genotoxic effects of crude liver oils from 3 species of Mediterranean sharks by means of in vitro micronucleus test using human lymphocytes].

Lymphoid system tumours have been identified in two subjects who used to handle for several years mediterranean shark liver oil and squalen extracted from this oil. Moreover, scientific data, reported in 1959 by Kröning, show the induction of lymphoid tumours in C57 B1 mice after exposure of their skin to squalen. These observations rose the question of a possible mutagenic power of shark liver oil. In order to determine the genotoxicity of these oils, in vitro assays have been performed on crude hepatic oil of three species of mediterranean sharks: two benthic sharks, Centrophorus granulosus and Galeus melastomus, and one pelagic specie, Prionace glauca. Genotoxicity of oils have been assayed using a micronucleus test which can detected simultaneously clastogen and aneugen effects. The incubation of human cells with the hepatic crude oils of Centrophorus granulosus increases the rate of the binucleated micronucleated cell in a dose dependent manner. The mean micronucleated cell rate was 9.0%. +/- 1.1 in controls and increased up to 27,1%. +/- 4,0 for the highest concentrations of oil extracts. Similar results have been obtained with crude hepatic oils of Galeus melastomus and Prionace glauca. The results of this experimental study show that the crude liver oils of three species of sharks are genotoxic and confirm a high carcinogenic risk.

Adult↗

[In vitro study of the antimutagenic activity of alphahederin].

Authors have studied the antimutagenic power of alphahederin (a saponin extracted from Hedera helix) versus a clastogenic agent, doxorubicin and an aneugenic agent, carbendazim. We have applied a protocol of incorporation of alphahederin (pretreatment, simultaneous treatment and post treatment) to determine a mechanism of action. According to this protocol, alphahederin induces a significant diminution of the rate of micronuclei wathever the phases of the protocol. These results demonstrate the antimutagenic activity of alphahederin with a mechanism of action, both desmutagenic and bioantimutagenic.

Air Pollutants, Occupational↗

[Cannabis: toxicokinetic focus and methodology of urinary screening].

Cannabis is the most commonly used illicit drug in the world. The major psychomimetic compound is delta 9-tetrahydrocannabinol. The major effects consist in alterations of sensory perception, cognition, motor coordination and self-perception. Procedures designed to detect cannabis use have been developed since 1988. The traditional approach is to screen urine by immunoassay and to submit positive samples for confirmation by gas chromatography and mass spectrometry. There continue to be many difficulties in interpreting the results because of the biotransformations of delta 9-tetrahydrocannabinol.

Cannabinoids↗

[Application of micronucleus test for the demonstration of antimutagenic properties of natural substances].

Authors have used a reliable and reproductible original model of controlled production of free radicals for the cytokinesis-block micronucleus assay. This mutagenicity test is of easy realization and quick interpretation. An experimental model is proposed to test mutagenic activity of free radical generators and antioxydant properties of many substances, such as ascorbic acid. Its addition to the culture medium showed a significant decrease in the rate of micronucleated cells exposed to the free radical generator. The study of other antioxydant compounds (beta-caroten and 5-hydroxyquinolin) have confirmed results previously obtained with ascorbic acid. Thus, the free radical generator coupled to the cytokinesis-block micronucleus assay represents a reliable test to study and evaluate the antioxydant power of natural substances.

Analysis of Variance↗

[Poisoning by anorexigenics. Information from the data bank of the Anti-Poison Center of Marseille (1973)].

Using the data bank developed by the Computer Service of the Lyon Hospitals, the Anti-Poisons Centre of Marseille presents an initial study of intoxications by appetite suppressants. The work was complemented by a simultaneous study using conventional manual techniques. An epidemiologic review of 1973 and an approximate assessment of toxic doses in the adult and child were possible. They should be of particular use in answering telephone enquiries at anti-poison centres.

Adolescent↗

[Doxorubicin and cisplatin genotoxicity: search for a real indication using the micronucleus test].

Doxorubicin and cisplatin are two major anticancer drugs, and are also known to be mutagen. Using short term mutagenesis tests, the cytokinesis-block micronucleus test and chromosome aberrations test, a study of the cytotoxicity and the mutagenicity of these two drugs has been aimed to determine a genotoxic of reference for these tests. Cisplatin and doxorubicin were genotoxic and gave positive results with the two tests. Since cisplatin was more cytotoxic than doxorubicin for a same genotoxicity, doxorubicin has been selected as a positive control for these two short-term mutagenesis tests. A study of the individual variability in the response to in vitro doxorubicin exposure was made using the cytokinesis-block micronucleus test, applied to cultured T lymphocytes form healthy subjects and cancer patients. Micronucleated cell rate before (T0) and after in vitro exposure to doxorubicin (T1) were determined in the two groups of subjects. Micronucleated cell rates T1 were significantly higher than T0 for healthy subjects and cancer patients. A calculated sensitivity index [(T1)-(T0)] is proposed to evaluate the individual sensitivity to the positive control doxorubicin.

Adult↗

[Genotoxic and clastogenic effects of doxorubicin].

Doxorubicine is an anthracyclin used widely in medical oncology. The purpose of this investigation was to evaluate the genotoxic and clastogenic effects of this substance through the cytokinesis-block micronucleus assay. This short-term mutagenicity assay is of easy realization and quick interpretation. It has enabled the demonstration of a significant decrease, after exposure of cells to doxorubicin, of the rate of micronucleated cells (average = 10.8 +/- 5.7 micronucleus versus 31.9 +/- 11.5 after exposure, p < 0.0001) and chromosomic aberrations (1 aberration for the control culture versus 17 since the first dose, p < 0.001). At the end of this study, the cytokinesis-block micronucleus assay represents a reliable test to study and evaluate the genotoxic power of some substances.

Adult↗