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Biomedical subjects

A M Rossi

Publications and source records attributed to A M Rossi.

At least 55 records · Page 3Linked to original sources
PubMed1983

Bone marrow cell chromosomal aberrations and styrene biotransformation in mice given styrene on a repeated oral schedule.

Styrene's capacity to induce chromosomal aberrations was studied in bone marrow cells of CD1 male mice. No mutagenic effect could be detected after either a 4-day treatment course with daily oral doses of 500 mg/kg or a 70-day course with daily oral doses of 200 mg/kg. Urinary elimination of styrene metabolites related to styrene-7,8-oxide formation (i.e. phenylethylene glycol, mandelic acid, benzoic acid, phenylglyoxylic acid and total mercapturic acids) was quantitatively evaluated in the group of mice given the 200 mg/kg dose. In parallel, kinetic studies were made on styrene and styrene-7,8-oxide blood concentrations in the same group of animals. These determinations were carried out on days 1 and 70 of treatment by spectrophotometric, gas chromatographic and mass fragmentographic procedures. Not even nanograms of styrene-7,8-oxide were found in the blood of styrene-treated mice. This suggests that the metabolite does not migrate from the cellular compartment where it is formed being immediately metabolized or irreversibly bound to cellular structures. This observation could well explain the lack of mutagenic effects observed.

Administration, Oral↗
PubMed1983

In vivo and in vitro mutagenicity studies of a possible carcinogen, trichloroethylene, and its two stabilizers, epichlorohydrin and 1,2-epoxybutane.

In vivo and in vitro methodologies that have employed the yeast Schizosaccharomyces pombe as genetic indicator have been utilized to investigate the mutagenicity of two trichloroethylene (TCE) samples of pure and technical grade. Mutagenicity assays were also performed on two stabilizers contained in the technical grade sample: epichlorohydrin and 1,2-epoxybutane. In the in vitro studies a metabolic conversion system was supplied by liver homogenate (S-9) from mice and rats untreated and pretreated with phenobarbital and/or beta-naphthoflavone. Up to highly toxic doses of TCE were applied to growing and stationary-phase yeast cells. In the in vivo studies two different host-mediated assays, intrasanguineous and intraperitoneal methodologies, were performed on different mice breeds treated by oral administration. Epichlorohydrin and epoxybutane were tested singly or combined in a mixture of the same ratio as in the technical grade TCE sample. Both TCE samples gave negative results for in vivo and in vitro assays, whereas the two contaminants were found mutagenic only in vitro. The high toxicity of the technical TCE sample did not allow us to reach concentrations containing effective levels of its two additives.

Animals↗
PubMed1983

Mutagenic relevance of rat hepatocyte nuclei in the activation and inactivation of xenobiotica. Cyclophosphamide and epichlorohydrin activity on the yeasts S. pombe and S. cerevisiae.

The influence on the mutagenicity of cyclophosphamide (Cy) and epichlorohydrin (ECH), of liver nuclei and hepatic post-mitochondrial (S9) preparations from phenobarbital-treated rats, was examined. The study was conducted in vitro, with 2 yeasts, Schizosaccharomyces pombe (P1 strain) which allows the detection of forward mutations, and Saccharomyces cerevisiae (D5 strain), in which the induction of different genetic effects, such as mitotic recombination, can be evaluated. The results indicated that the nuclear fraction has a qualitative capacity for biotransformation of compounds, overlapping that of S9. From a quantitative point of view, the Cy-activating capacity of the nuclear fraction was twice as high as that of S9 whereas the two fractions showed a similar ECH-inactivating ability. The present study strengthens the hypothesis of the relevance of nuclei as a site of metabolic activation and inactivation of exogenous compounds.

Animals↗
PubMed1983

Evaluation of epichlorohydrin (ECH) genotoxicity. Microsomal epoxide hydrolase-dependent deactivation of ECH mutagenicity in Schizosaccharomyces pombe in vitro.

The mutagenic effect of epichlorohydrin (ECH) on the yeast Schizosaccharomyces pombe was studied in vitro in the presence of mouse-liver S9 mix and microsomal and cytosolic fractions. The incubations were always performed in the absence of NADPH-generating systems. S9 mix and microsomes from phenobarbital-pretreated mice significantly reduced ECH mutagenicity, whereas the cytosol did not result in any deactivating effect. The various protein contents of the subcellular fractions were not involved in any scavenger effect as regards ECH mutagenic activity. Moreover, the addition of reduced glutathione to the incubation mixtures indicated that it did not play an important role, either per se or through the enzyme(s) glutathione-S-epoxide transferase(s), in preventing ECH genotoxicity. Our results suggest that microsomal epoxide hydrolase(s) represents the major step in the detoxifying pathway of ECH. These observations were supported by measurements of the specific epoxide hydrolase activity in the various fractions on the same substrate.

Ascomycota↗
PubMed1983

Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice.

Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-marrow cells of CD1 mice given single oral doses of 50 and 200 mg/kg in water. The ECH diol derivative (3-chloro-1,2-propanediol) was tested in vitro by a forward-mutation assay on the yeast Schizosaccharomyces pombe and showed a weak but significant mutagenic effect. The failure of ECH to induce mutagenic effects appears to be due to the rapid metabolic clearance of the compound in vivo. ECH blood kinetics at both doses, and at the same time the concentration of the diol, were determined. ECH rapidly disappeared from mouse blood, being no longer detectable 20 min after treatment. In contrast, 3-chloro-1,2-propanediol was measurable up to 5 h after dosage. No difference was observed in the kinetic and metabolic behavior of ECH after single and repeated doses (50 and 200 mg/kg/day for 7 days). When 3-chloro-1,2-propanediol was tested, neither glutathione depletion nor epoxide hydrolase inhibition (evaluated with both styrene-7,8-oxide and ECH as substrates) could be detected in mouse liver. Finally, no difference in ECH blood kinetics or metabolism were observed in experiments in which the compound was administered (200 mg/kg) intraperitoneally in water or orally as a solution in dimethyl sulfoxide.

Animals↗
PubMed1982

Mutagenic action of structurally related alkene oxides on Schizosaccharomyces pombe: the influence, 'in vitro', of mouse-liver metabolizing system.

A series of aliphatic epoxides were tested for their ability to induce forward mutations in the yeast Schizosaccharomyces pombe. For all the compounds under study, a linear dose-response relationship was found, and the ranking of the relative specific activity was: epichlorohydrin greater than ethylene oxide greater than glycidol greater than 1,2-epoxybutane greater than 1,1,1-trichloropropylene oxide greater than propylene oxide greater than 2,3-epoxybutane. The influence of the metabolic conversion of the epoxides by the mouse-liver S9 fraction was also investigated. In such conditions, except for the 2,3-epoxybutane, the genetic activity of epoxides seems to be reduced.

Animals↗
PubMed1978

Marihuana and mood in human volunteers.

Fifteen adult male marihuana smokers volunteered to live on a hospital research ward for a 31-day study which included a five-day baseline, a 21-day marihuana smoking period and a concluding five-day baseline. Subjects rated their moods and level of intoxication each day at scheduled occasions. Analyses of variance indicated a significant trend in the mood ratings which increased slightly in the euphoric direction just before smoking marihuana (compared to routine ratings) and further increased slightly after smoking marihuana. Level of intoxication ratings and mood ratings were not significantly correlated, but an intoxicated subject's mood ratings were significantly correlated with the average mood ratings of other subjects intoxicated or not. The results suggest that marihuana may increase a person's susceptibility to the moods of others and the feeling of being in harmony with others may be a positive reinforcer.

Cannabis↗
PubMed1977

Effects of marihuana on reaction time and short-term memory in human volunteers.

Twenty-seven adult male marihuana smokers volunteered to participate in a hospital research ward study for a 31-day period. Following five days of baseline acclimatization, subjects could purchase and smoke marihuana cigarettes on a free choice basis for a period of 21 consecutive days. The marihuana smoking period was followed by a concluding five-day baseline. Measurements of simple reaction time, choice reaction time and short-term memory were carried out during the entire study. Analysis of variance revealed no statistically significant differences between control and marihuana performance; however, a correlational analysis showed that individual subject performances on all three tasks were significantly correlated from test session to test session during control conditions but not during marihuana smoking conditions. Findings are discussed in relation to attentional and motivational factors associated with performance on the three tasks.

Adult↗
PubMed1977

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↗
PubMed1976

Evaluation of the genetic effects induced by vinyl chloride monomer (VCM) under mammalian metabolic activation: studies in vitro and in vivo.

As part of a programme of investigations on the biological effects of the industrial compound vinyl chloride monomer (VCM), the raw material for the production of polyvinyl chloride (PVC), analyses on the genetic effects by this compound have been done by experiments (in vitro) which have taken mammalian metabolism into account. Vinyl chloride in the presence of purified microsomes (sedimented at 105,000 g) obtained from mouse liver was converted into an active metabolite(s) which produced gene mutations in the yeast Schizosaccharomyces pombe (forward mutation) and gene conversions in two loci of a diploid Saccharomyces cerevisiae. Moreover, the compound was active in the host-mediated assay, when mice were treated with an oral dose of 700 mg/kg. The role is discussed of mutagenicity tests for the prediction of both genetic and carcinogenic risks of chemical compounds in industrial use.

Animals↗
PubMed1976

Mutagenicity of industrial compounds: styrene and its possible metabolite styrene oxide.

Styrene and its presumed metabolite, styrene oxide, were tested for their mutagenic effect on a forward mutation system of yeast and of Chinese hamster cells, and on a gene-conversion system of yeast. Experiments with liver microsomal preparations and host-mediated assay with yeast were also carried out. Styrene oxide was mutagenic in all test systems. Styrene was mutagenic only in the host-mediated assay.

Adenine↗
PubMed1975

Mutations induced by X-radiation in the yeast Schizosaccharomyces pombe.

Experiments on strains of yeast with different genetic backgrounds were done to evaluate the kinetics of inactivation and mutation induction by X-radiations. A system of forward mutation induction in five loci was used as a specific mutation rate of 0.14-10-minus 8 times locus times rad was evaluated for the wild type. From a comparison of observations with wild type and radiation-sensitive strains, it may be assumed that, in this yeast, mutations are mainly the result of a repair-active process. The range of genotypic and phenotypic influence upon the specific locus mutation rate was evaluated with appropriate biological material and experiments.

Ascomycota↗