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Biomedical subjects

C Corsi

Publications and source records attributed to C Corsi.

At least 73 records · Page 4Linked to original sources

[Levels of xenobiotic metabolizing enzyme activities of xenobiotic tissue in different animal species].

Aminopyrine-N-demethylase, p-nitroanisole-O-demethylase and lipid peroxidation were determined in liver postmitochondrial fractions (S-9) of mice in the basal state and after induction with beta-naphtoflavone, sodium phenobarbital, or both the inducers. The two activities were similar in their response to all inductions: meanly, 1,2 times with beta-NF, 2,0 times with Na-PB, 5,8 times with Na-PB+ beta-NF. Lipid peroxidation was sensibly more active in basal animals with respect to that with induction. The results are discussed in a partial review of the sector literature, which deserves still much work to be completed.

Aminopyrine N-Demethylase↗

[Genetic activity of 1,2-dichloroethylene. A). In vitro studies].

1,2-dichloroethylene cis and trans were tested for their ability to induce point mutation, mitotic gene conversion and mitotic recombination in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in a suspension test with and without a mammalian microsomal activation system. In this test 1,2-DCE cis and trans were toxic but not genetically active even with S9 activation.

Dichloroethylenes↗

[Genetic activity of 1,2-dichloroethylene. B). In vivo studies: effect on microsomal enzymes].

Mutagenicity study "in vivo" (Intravenous host mediated assay) confirms suspension test results with cis- and trans -1,2-dichloroethylene: no genetic effects could be detected. Single and repeated doses of trans-1,2-DCE induced liver aminopyrine demethylase and cytochrome P-450 whereas the cis- isomer decreased them. Similar results were obtained after induction with phenobarbital + beta-Naphthoflavone.

Aminopyrine N-Demethylase↗

Studies on microsomal metabolizing systems for mutagenesis tests. Stability of fortified fractions.

Rat liver S-9 microsomal fractions were fortified with NADP+, G-6-P, and MgCl2 and stored at -80 degrees C and -20 degrees C. At various times aminopyrine demethylase and lipid peroxidation were determined and compared with that of non-fortified fractions. No difference in stability was noted between fortified and not fortified fractions. The known stability pattern of non fortified fractions was confirmed. Lipid peroxidation was found blocked in the fractions stored at -80 degrees C whereas a small release of malonyl dialdehyde proceeded in the frozen state at -20 degrees C, contributing to the loss of activity at this temperature. The use of pre-fortified fractions stored at -80 degrees C is justified.

Aminopyrine N-Demethylase↗

Studies on the incubation mixtures for the in vitro mutagenesis test with metabolic activation (microsomal assay) = 2. Behaviour of cytochromes P-450, P-420, b5, of NADPH-CYT. C-reductases, and p-nitroanisole demethylase.

Cytochromes P-450, P-420, b5, NADPH-cytochrome c-reductase, aminopyrine and p-nitroanisole demethylase and lipid peroxidation were determined at various times in the incubation mixtures for the in vitro microsomal assay for the mutagenic activity of xenobiotics. No effect was observed on cytochromes b5 and P-420. A decrease in cytochrome P-450 (about 50% in 2 hrs.) and a much faster decrease of aminopyrine demethylase and NADPH cytochrome c-reductase (about 50% in 30 min) was noted with mice microsomes. With S9 liver fraction of rat, p-nitroanisole demethylase activity was much more stable than aminopyrine demethylase activity in the presence of lipid peroxidation, but the decrease was faster and at comparable rates for both activities in the presence of 50 mM styrene. The use of simple colorimetric assay as proves of microsomal monooxygenase activity and the importance of this kind of enzyme studies for a better understanding of the in vitro mutagenesis results are discussed.

Animals↗

[Role of cytochrome P-450 in strain D7 of the yeast Saccharomyces cerevisiae].

Usual "in vitro" mutagenesis tests combine microbial test systems with mammalian metabolism (microsomal assay). Some cases are known in which expected positive results are not obtained due to many factors operating between the microsomes in the incubation mixtures and the nucleus of the test microbial cells (detoxifying mechanisms, permeability effects, unstable intermediate, alternative targets in the pathway, etc.). In these cases, useful additional information could be obtained using microbial test systems with incorporated metabolism. Microbial systems and in particular yeasts in Cytochrome P-450 dependent metabolizing activity are known since many years. We studied under this aspect the strain D7 of Saccharomyces cerevisiae, used in our laboratory, in order to standardize the conditions for optimal metabolizing activity. The composition of the culture medium, the growth phase, and the effect of the amount of the initial inoculum, were studied. Cytochrome P-450 content was determined by the technique of difference spectra (reduced cytochrome +/- CO). Results on the effect of glucose and sodium phenobarbital concentration in the culture medium were in agreement with the literature. Moreover we found that the cytochrome P-450 contents was markedly dependent on the size of the initial inoculum, being higher and the smaller was the initial inoculum.

Cell Division↗

Genetic activity of vinylidene chloride in yeast.

Vinylidene chloride (VDC) was tested for its ability to induce both point mutation and mitotic gene conversion in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in a suspension test with and without a mammalian microsomal activation system, and in the intrasanguineous host-mediated assay in mice. In suspension tests with D7, VCD was toxic but not genetically active without microsomal activation. When a mouse liver 10 000 X g supernatant was included in the suspension tests, dose-related increases in both point mutation and mitotic gene conversion were seen at survival levels greater than 50%, at doses of VCD above 20 mM. In the host-mediated assay, VDC induced both point mutation and mitotic gene conversion when recovered from the liver and kidneys after both acute and sub-acute dosing. Yeasts recovered from the lungs showed little, if any, increase in either point mutation or mitotic gene conversion.

Animals↗

The problem of negative results for styrene in the in vitro mutagenesis test with metabolic activation (microsomal assay). - 2. Behaviour of epoxide hydrolase in the incubation mixtures.

The behaviour of epoxide hydrolase and monooxygenase was studied in incubation mixtures for the in vitro mutagenesis test with metabolic activation (microsomal assay) both in the presence and in absence of styrene 50mM. Epoxide hydrolase activity was much more stable than monooxygenase in all tested systems (S-9 fractions or microsomes of rats or mice, males or females) both in the presence and in absence of styrene. Membrane bound epoxide hydrolase was slightly less stable than the soluble one. These results further substantiate the explanation for the negative results of in vitro mutagenesis tests with styrene.

Aminopyrine N-Demethylase↗

Genetic effects of vinylcyclohexene diepoxide in yeast.

Using D7 strain of S. cerevisiae where we can consider three genetic effects such as mitotic gene conversion, mitotic cross over and reverse mutation we tested vinylcyclohexene diepoxide "in vitro" without metabolic activation. In this condition VCD is very toxic and induces both three genetic effects namely mitotic gene conversion, mitotic cross over and reverse mutation.

Crossing Over, Genetic↗

[Use of the D7 strain of S. cerevisiae in the determination of environmental risk. 1. Genetic effects of trichloroethylene].

Trichloroethylene (TCE) was tested for its ability to induce both point mutation and mitotic gene conversion in diploid strain of yeast. S. cerevisiae (strain D7) was tested for both activities in culture with and without a mammalian microsomal activation system and intrasanguinous host-mediated assay in mice. In suspension test with D7, TCE was genetically active only with microsomal activation. In vivo TCE induced both point mutation and gene conversion in D7 and gene conversion in D4 when recovered from the liver and kidneys after both acute and subacute dosing. Yeasts recovered from the lungs showed little, if any, increase in genetic effects.

Animals↗

[Use of the D7 strain of S. cerevisiae in the determination of environmental genetic risk. 2. Genetic effects of procarbazine].

Procarbazine was tested in vitro without and with S-10 fraction from mice liver (microsomal assay) using Saccharomyces cerevisiae strain D7, Salmonella typhimurium (strains TA 98, TA 100, TA 1535) and in vivo in Swiss albino mice (host mediated assay) using D7. Procarbazine without S-10 fraction was highly toxic and induced mitotic cross-over, gene conversion, and reverse mutation in D7. It had a toxic effect on all the Salmonella strains, but it did not induce any reverse mutations of the histidine mutants. In host-mediated assay using Saccharomyces, there was no genetic effect found in the indicator organism.

Animals↗

The problem of negative results for styrene in the in vitro mutagenesis test with metabolic activation (microsomal assay):explanation by gas chromatographic analysis.

Mutagenic experiments in vitro were performed on yeast (S. pombe) with styrene with metabolic activation by adding at fixed times fresh mouse microsomes to the incubation mixture. Preceding studies with a single initial addition of microsomes were negative up to the maximal dose of 100 mM styrene for 60 min (5). The addition of fresh microsomes at the times 12, 24, 36 and 48 min in the presence of EDTA 40 mM resulted in an increased toxicity of styrene in vitro, but not in increased mutagenicity. Gas chromatographic determination of styrene oxide in the incubation mixture with 50 mM styrene revealed a concentration of active metabolite not capable of acting mutagenically.

Ascomycota↗

The use of organic solvents in mutagenicity testing.

13 organic substances (dimethylsulfoxide, methanol, ethanol, n-propyl alcohol, sec-butyl alcohol, tert-butyl alcohol, dl-sec-amyl alcohol, ethylene glycol, ethylene glycol monomethyl ether, 1,4-diethylene dioxide, acetone, methyl acetate and formamide) were considered from the standpoint of their use as solvents for water-insoluble chemicals to be tested for mutagenicity. First, the effect of these solvents on cell survival was studied in the yeast Schizosaccharomyces pombe and in V79 Chinese hamster cells. 8 solvents showing relatively low toxicity on either cell system (dimethylsulfoxide, ethanol, ethylene glycol, ethylene glycol monomethyl ether, 1,4-diethylene dioxide, acetone, methyl acetate and formamide) were tested for their effect on aminopyrine demethylase. 4 solvents (ethanol, 1,4-diethylene dioxide, methyl acetate and formamide) showed a more or less pronounced adverse effect on the microsomal enzymic activity. The remaining 4 and methanol (whose effect on aminopyrine demethylase was not testable) were assayed for mutagenicity in S. pombe. They all gave negative results both with and without the post-mitochondrial fraction from mouse liver.

Animals↗

Studies on the incubation mixtures for the in vitro mutagenesis test with metabolic activation (microsomal assay). Behaviour of mixed function oxidase and lipid peroxidation in the presence of some xenobiotics.

The effect of some xenobiotics on microsomal mixed function oxidase and lipid peroxidation, in mice, in incubation mixtures for the in vitro mutagenesis test with metabolic activation was studied. Aniline 1 or 2 mM and aminopyrine 0.38 or 8.33 mM completely inhibited the lipid peroxidation with small protection of the monooxygenase. Styrene 50 or 100 mM inhibited to a lesser extent the lipid peroxidation with marked increase in the inactivation of the monooxygenase. By a technique based on successive additions of fresh microsomes it was possible to evaluate the part of the inactivation due to enzyme denaturation and that due to inhibition. EDTA 40 mM was not able to protect from inactivation in the presence of aniline 1mM. Data of this type could be utilized to obtain more reliable results of in vitro mutagenesis tests with metabolic activation by suitably managing the enzyme activity in the incubation mixtures in order to keep it as constant as possible.

Aminopyrine↗

Reactive hyperemia in Raynaud's disease.

We studied reactive hyperemia after ischemia, after cold, and after cold plus ischemia, in normal subjects, in fingers with Raynaud's phenomenon, and in fingers without Raynaud's phenomenon in hands where other fingers were affected by Raynaud's phenomenon. The results obtained demonstrate the existence of a criohyperdysestesia both in fingers with Raynaud's phenomenon and in fingers without Raynaud's phenomenon in hands where other fingers are affected by it.

Cold Temperature↗

Induction of gene mutations and gene conversions by vinyl chloride metabolites in yeast.

Chloroethylene oxide and 2-chloroacetaldehyde, two metabolites of vinyl chloride, and 2-chloroethanol, a putative metabolic intermediate, were assayed for their genetic activity in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Chloroethylene oxide was found to be the most effective in inducing forward mutations in Sch. pombe and gene conversions in S. cerevisiae, increasing the mutation and conversion frequencies 340 and 50 times, respectively, over those of the controls. In either the presence or the absence of mouse liver microsomes, 2-chloroacetaldehyde showed only feeble genetic activity, and 2-chloroethanol was completely inactive in both yeast strains. In contrast to vinyl chloride, 2-chloroacetaldehyde did not induce forward mutations in Sch. pombe inthe host-mediated assay in mice. The results strongly support the hypothesis that chloroethylene oxide is one of the principal mutagenic agents formed from vinyl chloride in the presence of mouse liver enzymes.

Acetaldehyde↗