Biomedical subjects
Publications and source records attributed to M Mercier.
The results obtained by testing the mutagenicity of several vinylic monomers, styrene, butadiene, acrylonitrile, vinyl chloride on strains of Salmonella typhimurium in various experimental conditions, modes of incubation, and in the presence of different metabolic activating systems, demonstrate that these parameters have a variable effect on the mutagenic potency of those monomers.
The mutagenicity of 19 herbicide-derived chlorinated azobenzenes and structurally related chlorinated anilines and nitrobenzenes was assayed towards several strains of S. typhimurium, using the plate incorporation method and the fluctuation test, in the presence or in the absence of liver post-mitochondrial fractions, in aerobic and anerobic conditions. Positive results were obtained with 4,4'-dichloroazobenzene, 4,4'-dichloroazoxybene, 3,4-dichloronitrobenzene and, to a much lesser extent, with 3,4,3',4'-tetrachloroazobenzene. No mutagenic effect was observed with 2,3,7,8-tetrachlorodibenzo-p-dioxin in any condition.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Urines collected from rats and mice treated with acrylonitrile (ACN) were mutagenic towards Salmonella typhimurium strain TA 1530 in the absence of a metabolic activation system. When assayed in the presence of a liver S9 mix, this activity was suppressed when the urines were obtained from acrylonitrile treated rats, and decreased when these urines were collected from acrylonitrile treated mice. Pretreatment of the animals with phenobarbital abolished the direct mutagenicity of urines from acrylonitrile treated rats, and reduced that observed with mice urines. Addition of beta-glucuronidase to the incubation mixtures enhanced the mutagenicity of the urines from both phenobarbital untreated and treated rats and mice injected with acrylonitrile.
Many reports in the literature have indicated that the guinea-pig is resistant to the carcinogenic effect of N-2-fluorenylacetamide (2FAA); this refractoriness has been attributed to its lack of N-hydroxylating enzymes. The present communication, however, supports the results of contradictory reports which demonstrate that guinea-pig liver microsomes are in fact able to N-hydroxylate both 2-fluorenamine and 2FAA. The guinea-pig N-hydroxylase activity toward 2-fluorenamine is found to be even greater than the reported activity in the rat and hamster. It is similarly inhibited by 3-methylcholanthrene (3MC), 7,8-benzoflavone (7,8 BF) or miconazole. Activity toward N-2-fluorenacetamide is present in the microsomal preparation from the control guinea-pig. There is slight activation by SKF525A, paraoxon (PX) or sodium fluoride. Under optimum conditions, in the presence of both paraoxon and sodium fluoride, activity is equivalent to that of rat liver microsomal enzymes.
The kinetic properties of the N-hydroxylation of 2-acetylaminofluorene (2-AAF) are studied with microsomal preparations of livers from both control and 3-methylcholanthrene (3-MC)-pretreated rats and hamsters. The level of basal enzymatic activity is higher in hamster than in rat liver; 3-MC induces the activity in both animals. When added in vitro to incubation mixture, 3-MC competitively inhibits the N-hydroxylase activity. When fed to rats simultaneously with 2-AAF, 3-MC suppresses the carcinogenicity of the acetylated arylamine by inhibiting the first step in its activation pathway. Hamster tissues are not protected by this pretreatment because the level of N-hydroxylase activity is too high.
Gaseous butadiene (BUT) was mutagenic towards S. typhimurium strain TA 1530 when the incubation mixture was supplemented with a NADPH-fortified rat liver microsomal preparation; mutagenicity increased with the dose. A significant mutagenic effect was similarly observed when the petri dishes, containing the bacteria but no metabolic activation system, were incubated in the presence of butadiene, in a desiccator in which plates containing the S-9 rat liver fraction had been placed. This indirect mutagenic effect was attributed to the formation, by the S-9 mix, of volatile intermediate(s) that migrated and induced mutations in neighbouring bacteria.
The effects of temperature on amylase secretion in vitro have been measured under stimulated and nonstimulated conditions. In both cases a very rapid decrease of secretory rate was observed between 37 and 25 degrees C (60-70%). The decrease is less pronounced between 25 an 15 degrees C. Between 15 and 13 degrees C a drop of secretory activity (10%) was observed under stimulation whereas an increase was measured in absence of stimulus. At lower temperatures the rate of secretion falls again abruptly. These results show that the secretory pattern of amylase from pancreas in vitro as a function of temperature is very different under stimulated and nonstimulated conditions. We suggest that the abrupt change of secretory activity between 15 and 13 degrees C could correspond to a change of physical state of the membranes involved in the exocytosis process.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
By applying a new and highly sensitive assay for measuring N-hydroxy metabolites, the biochemical properties of the microsomal N-hydroxylase from control and 3-methylcholanthrene-treated rat and hamster liver have been analyzed, and the following conclusions have been drawn. (a) Due to a difference in enzyme affinity, the metabolic activation of acetylaminofluorene is more pronounced than that of aminofluorene, a fact which correlates with the difference in the carcinogenic potency of the two compounds. (b) Arylamine N-hydroxylase differs qualitatively as well as quantitatively from arylamide N- hydroxylase mainly in terms of sensitivity to various in vitro inhibitors. (c) 7,8-Benzoflavone and 3-methylcholanthrene are strong inhibitors of liver microsomal N-hydroxylases. This effect could partly explain the inhibition of the hepatic tumorigenicity of acetylaminofluorene in animals simultaneously fed 3-methylcholanthrene. (d) The metabolism of acetylaminofluorene proceeds via both ring- (C-1, C-3, C-5, or C-7) and N-hydroxylation. There is clear reciprocal interaction between these various microsomal pathways. (e) The apparent increase in Km following pretreatment of the rat with 3-methylcholanthrene is due to competitive inhibition of the N-hydroxylase by some of the C-hydroxy metabolites. This effect is not seen in hamster liver.
A method is described that allows for alternate operation of a "pin and cup"-type electron-capture detector (ECD) in the normal ECD mode and in the metastable argon ionization mode. By such means, marker n-alkanes can be run without a change of the gas or temperature parameters, and measurements can be made of the Kováts retention indices of unknown compounds that are detectable in trace amounts by ECD only. As an application, tests are reported which support the probable enzymatic conversion of 3,4-epoxy-1-butene into diepoxybutane during incubation of the former with rat liver microsomes.
Explore the source record for details and available documents.
The kinetic parameters of liver microsomal vinyl oxide synthetase as well as their modifications under the influence of various pretreatments have been evaluated, using 1,1,2-trichlorethylene (TCE) as a substrate. The results were correlated with those obtained using aldrin oxide synthetase and benzpyrene hydroxylase as typical cytochrome P-450 dependent enzymatic activity. The treatments of animals with chemical carcinogens selectively increase the affinity of those enzymes for their substrates.
Explore the source record for details and available documents.
Explore the source record for details and available documents.