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A Carere

Publications and source records attributed to A Carere.

At least 19 recordsLinked to original sources
PubMed1992

Further in vitro and in vivo mutagenicity assays with thiram and ziram fungicides: bacterial reversion assays and mouse micronucleus test.

The fungicides thiram and ziram have been assayed in a battery of nine bacterial strains of different genetic specificity. The results obtained suggest the induction of excisable DNA lesion(s), and indicate similar mutability of strains with AT or GC base pairs at target sites. This mutagenic profile is clearly distinct from that of oxidative mutagens, and it does not support the proposed role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in bacteria. Furthermore, the bone marrow micronucleus test has been carried out in B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5-50 mg/kg) and ziram samples (2.5-10 mg/kg in males, and 5-20 mg/kg in females). Thiram produced a significant increase of micronucleated PCEs in male mice sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase was detected in treated females. Ziram, tested in a lower range of doses because of its higher toxicity, resulted negative in both sexes. Both the acute toxicity and the ratio polychromatic/normochromatic erythrocytes indicated some sex specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1 mouse.

Animals↗
PubMed1992

The induction of mitotic chromosome malsegregation in Aspergillus nidulans. Quantitative structure activity relationship (OSAR) analysis with chlorinated aliphatic hydrocarbons.

The biological activity of 24 chlorinated aliphatic hydrocarbons has been studied in the mold Aspergillus nidulans. The ability to induce chromosome malsegregation, lethality and mitotic growth arrest has been experimentally determined for each chemical. These data, together with those of 11 related compounds previously investigated, generated a data base which was used for quantitative structure-activity relationship (QSAR) analysis. To this aim, both physico-chemical descriptors and electronic parameters of each compound have been calculated and included in the analysis. The QSAR analysis indicated that toxic effects induced by chlorinated aliphatics in A. nidulans are mainly dependent on steric factors, as indicated by the correlation with molar refractivity (MR). Conversely, the ease with which they accept electrons, parametrized by LUMO (energy of the lowest unoccupied molecular orbital), plays a prevailing role in determining the aneuploidizing properties. An involvement of free radicals, generated by the reductive metabolism of haloalkanes, is hypothesized as an explanation of the data.

Aneuploidy↗
PubMed1991

Mutagenicity spectra in bacterial strains of airborne and engine exhaust particulate extracts.

The mutagenicity spectra of the organic extracts of both airborne particulate matter and diesel and gasoline soot particles were determined using a battery of 9 bacterial strains of different genetic specificity. The assays with crude extracts and with fractionated acidic, neutral and basic components revealed striking differences in the patterns of mutagenic responses produced by each of the complex mixtures investigated. The mutagenicity of air particulate matter was shown to depend mainly on direct-acting acidic and neutral compounds, with a lesser contribution of basic promutagens which required exogenous metabolic activation by liver S9. The assays with a diesel soot extract indicated the prevailing contribution of direct-acting acidic and neutral compounds, and suggested an important role also for nitro derivatives other than nitropyrenes. The gasoline exhaust was characterized by powerful promutagenic compounds, belonging to either the acidic, neutral or basic fractions. The implications of these results are discussed with respect to the contribution of engine exhausts to air pollution, and the possible use of mutagenicity spectra in the analysis of environmental complex mixtures.

Air Pollutants↗
PubMed1991

Further studies on the comutagenic activity of cigarette smoke condensate.

The comutagenic effect exerted by cigarette smoke condensate (CSC) was investigated. In vitro experiments with Salmonella typhimurium strains TA98 and TA98/1.8DNP6 indicated that CSC specifically enhances the mutagenicity of polyaromatic amines such as 2-aminofluorene, 2-acetylaminofluorene, 4-acetylaminofluorene and 2-aminoanthracene. The pattern of comutagenicity of CSC was shown to differ from that of norharman, a tobacco-related known comutagenic substance. Both black and blond tobacco CSCs proved to interact synergistically with 2-aminoanthracene mutagenicity. Chemical fractionation of CSC indicates the occurrence of comutagenic substance(s) in both neutral and basic components. Further in vitro experiments with 2-acetylaminofluorene metabolites and derivatives suggest that the comutagenic effect of CSC could involve later step(s) in the metabolic activation of fluorenylamines, i.e., the conversion of hydroxylamines into ultimate reactive species. The possible occurrence of a synergistic interaction of CSC with chemical mutagens in vivo was evaluated. Administration of 2-aminoanthracene/CSC mixtures, previously shown to be comutagenic in vitro, failed to demonstrate a synergistic effect in SCE induction in bone marrow cells of mice. This apparent discrepancy may rely on divergences in the activation pathways of polycyclic amines in vitro and in vivo.

2-Acetylaminofluorene↗
PubMed1991

In vitro studies with nine known or suspected spindle poisons: results in tests for chromosome malsegregation in Aspergillus nidulans.

Within the framework of a coordinated collaborative study for evaluating assays for aneuploidy, nine known or suspected spindle poisons were tested in mitotic segregation assays with Aspergillus nidulans. Experiments with A. nidulans diploid strain P1 revealed a statistically significant increase of whole chromosome segregants (non-disjunctional diploids and haploids) after treatments with chloral hydrate (CH), thiabendazole (TB), thimerosal (TM) econazole (EZ) and hydroquinone (HQ). The latter two chemicals also increased the frequency of mitotic cross-overs. Colchicine (COL), diazepam (DZ), cadmium chloride (CD) and pyrimethamine (PY) were ineffective. Further experiments with CH, TB, TM and EZ in the haploid strain 35 demonstrated that CH, TB and TM induced hyperploid types, thus indicating a primary effect on chromosome segregation in A. nidulans. However, since EZ did not induce putative hyperploids in strain 35 and trisomics in diploid 31, it is suggested that EZ affects chromosome segregation by an indirect mechanism, possibly related to induced structural chromosome damage, as previously shown for HQ.

Aneuploidy↗
PubMed1990

Strategies and governmental regulations.

An overview of testing strategies for the detection of genotoxins under OECD Guidelines and the EEC Directive 79/831 (VI Amendment) is outlined. The viewpoint of the Italian National Advisory Committee on Toxicology is also presented. In this context, the main issues of Genetic Toxicology (e.g., role of tests, tests recommended, classification of mutagens) are discussed.

Animals↗
PubMed1990

Chloroacetaldehyde is a powerful inducer of mitotic aneuploidy in Aspergillus nidulans.

The vinyl chloride metabolite chloroacetaldehyde (CAA) was tested for the induction of mitotic chromosome malsegregation in Aspergillus nidulans. Exposure of germinating conidia to CAA (16-64 microM) produced high rates of abnormal colonies with segregation of the whole first chromosome in the diploid strain P1, and abnormal, putative hyperploids in the haploid strain 35, indicating that CAA primarily induces abnormal chromosome segregation. Comparative assays with the known spindle poison chloral hydrate (CH), active in the dose range 6-10 mM, highlighted the unusual effectiveness of CAA in aneuploidy induction (the lowest effective concentration was 16 microM). Experiments on brain tubulin polymerization revealed an inhibitory effect by CAA only at concentrations 100-fold higher than those active in the induction of chromosome misdistribution in A. nidulans, possibly suggesting the involvement of alternative targets in its mechanism of action.

Acetaldehyde↗
PubMed1990

Microbial mutagenicity screening of natural flavouring substances.

Sixty-five commercial samples of natural flavouring substances were screened for mutagenicity in the Salmonella typhimurium strains TA98 and TA100. The results obtained demonstrated a significant mutagenic activity in onion and garlic extracts, both in assays with and without exogenous metabolic activation. The response pattern obtained in tester strains with different genetic backgrounds suggests the involvement of mutagenic flavone(s) in the genotoxic effects observed.

Allium↗
PubMed1989

A comparative study on ethanol and acetaldehyde as inducers of chromosome malsegregation in Aspergillus nidulans.

The activity of ethyl alcohol and acetaldehyde on mitotic chromosome segregation and conidial germination in Aspergillus nidulans was studied. Ethanol effectively induced malsegregation in a narrow range of concentrations (4.5-5.5%, v/v) and was inactive at doses which arrested conidial germination (above 6%). The same bell-shaped dose-response curve was shown by the spindle poison chloral hydrate, which was active in the range 6-10 mM. Acetaldehyde displayed a diphasic dose-response curve. Genetic analysis of induced segregants suggests that the disturbance of chromosome segregation is the primary genetic effect at low doses (0.025-0.037%), while at higher doses (above 0.1%), when growth was arrested, chromosome damage was primarily induced. The same pattern of segregants was produced by hydroquinone, a substance which indirectly affects chromosome segregation in A. nidulans. These differences in the genotoxic profiles of ethanol and acetaldehyde suggest that the effect exerted by ethanol on A. nidulans mitosis is not dependent on its conversion into acetaldehyde. In the absence of an effect of ethanol on in vitro polymerization of tubulin (actively inhibited by acetaldehyde at doses above 0.075%), a direct effect of ethanol on cell membranes is hypothesized. Comparison of the inhibition of growth and the effectiveness in aneuploidy induction displayed by ethanol, methanol, n-propanol and n-butanol demonstrates, in fact, a fair correlation with logP, a descriptor of lipophilicity related to the partitioning of compounds in biological membranes.

Acetaldehyde↗
PubMed1989

Genetic toxicology of 1,1,2-trichloroethylene.

1,1,2-Trichloroethylene (TCE) is a widely used halogenated solvent, produced in hundreds of millions of kg each year for industrial purposes. Occupational and environmental exposure of human populations to TCE has been reported in industrialized areas. Long-term carcinogenicity studies in rodents demonstrate that exposure to high doses of TCE results in the induction of liver and lung tumors in the mouse, and tumors of the kidney and the testis in the rat. An indirect mechanism, based on the stimulation of liver peroxisome proliferation by TCE metabolites, was proposed to explain species differences in TCE hepatocarcinogenicity. Mutagenicity studies indicate that TCE is weakly active both in vitro, where liver microsomes produce electrophilic TCE metabolites, and also in vivo in mouse bone marrow, where high rates of micronuclei, but no structural chromosome aberrations, are found. Among TCE metabolites, trichloroacetic acid was reported to be carcinogenic to mouse liver. Furthermore, both trichloroacetic acid and chloral hydrate were found to be genotoxic in vivo, inducing structural and numerical chromosome abnormalities, respectively.

Animals↗
PubMed1989

Regulatory aspects of chemical mutagenesis in Italy and in the European Community.

The first part of this paper outlines the guidelines on mutagenicity testing recommended in Italy by the National Advisory Committee on Toxicology. Thereafter, there is a description of the current Italian situation regarding the mutagenicity testing requirements for new chemicals of different use, which also takes into account the European Community approach and its legal implements (directives and recommendations).

Chromosomes↗
PubMed1988

Induction of chromosome malsegregation by halogenated organic solvents in Aspergillus nidulans: unspecific or specific mechanism?

Three chloromethanes (dichloromethane, chloroform and carbon tetrachloride) and 8 chlorinated ethanes (1,1- and 1,2-dichloroethane, 1,1,1- and 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane, pentachloroethane and hexachloroethane) were assayed in tests for the induction of mitotic segregation in Aspergillus nidulans diploid strain P1. Eight of the 11 compounds assayed (dichloromethane, chloroform, carbon tetrachloride, 1,1- and 1,2-dichloroethane, 1,1,2-trichloroethane, 1,1,1,2- and 1,1,2,2-tetrachloroethane) significantly increased the frequency of morphologically abnormal colonies which produced euploid whole-chromosome segregants (haploids and non-disjunctional diploids). Only in one case (1,1,1,2-tetrachloroethane) was a borderline increase in crossing-over frequency observed, thus suggesting the involvement of non-DNA targets in aneuploidy induction by these chlorinated hydrocarbons. Conclusive evidence for the induction of aneuploidy as the primary genetic event was provided by experiments in haploid strain 35 with 1,2-dichloroethane and 1,1,1,2-tetrachloroethane. Mutagenic, lethal and growth-arresting activities were quantitatively estimated and compared to a series of descriptors of physical and chemical properties of the molecules by means of multivariate statistical analysis. Lipophilicity, known to be related to c-mitotic activity, did not show any significant relationship with aneuploidizing activity, whereas a possible correlation among physico-chemical descriptors and toxic properties of test chemicals was highlighted.

Aneuploidy↗
PubMed1988

In vitro and in vivo mutagenicity studies with airborne particulate extracts.

The contribution of nitro compounds to airborne particulate mutagenicity was studied with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8DNP6. The results obtained indicate that nitropyrenes play a minor role in air particulate mutagenicity. Seasonal variations indicate a relatively greater contribution of nitro compounds to the mutagenicity of spring and summer samples. Fractionation of extracts into acidic, neutral and basic components shows that neutral compounds account for about two-thirds of the total mutagenic activity. Attempts to extract mutagens adsorbed onto particulate matter with aqueous media were almost completely negative. No significant mutagenicity was detected in urine and faecal extracts and in plasma samples of Sprague-Dawley rats treated with air particulate extracts at 80 mg/kg either per os or by i.p. injection. Negative results were obtained in the micronucleus test with Swiss mice treated at 200 and 400 mg/kg (twice by i.p. injection). A significant decrease in liver aminopyrine-N-demethylase was observed in Swiss mice injected with air particulate extracts or its basic and neutral fractions. In vitro experiments suggest a direct interaction of test materials with microsomal cytochrome P-450.

Aerosols↗
PubMed1988

Evaluation of the mutagenic activity of leucinostatins, a novel class of antibiotic peptides produced by Paecilomyces marquandii, in the modul Aspergillus nidulans.

Leucinostatins A, B, C, D, E, G, H, and K were thoroughly investigated for their genotoxic activity using the modul Aspergillus nidulans as the test organism. The results of assays for gene mutation (8-azaguanine resistance and methionine suppressors), gene conversion, mitotic crossing-over and mitotic aneuploidy induction suggest that these peptide antibiotics lack significant mutagenicity and that non-genotoxic mechanism(s) underlie their cytotoxic properties.

Anti-Bacterial Agents↗
PubMed1987

Urinary and faecal mutagenicity in Sprague-Dawley rats dosed with the food mutagens quercetin and rutin.

The natural flavonoid quercetin was administered to Sprague-Dawley rats by ip injection or gastric intubation of a single dose of 500, 1000 or 2000 mg/kg body weight. Mutagenicity assays with Salmonella typhimurium strain TA98 showed moderate mutagenic activity in the urines and faecal extracts but not in plasma samples from the treated animals. The mutagenic activity detected in the urines accounted for about 0.5% of the administered dose, irrespective of the route of administration and the dose level. Higher mutagenicity was demonstrated in faecal extracts. Rutin (quercetin-3-O-rutinoside) was administered by gavage and ip injection at 2000 mg/kg. Although the chemical was inactive as a mutagen in vitro, significant mutagenicity was detected in the urines and faecal extracts of the treated rats. Such activity was similar to that detected after administration of free quercetin in a dose some four times lower (by weight).

Animals↗
PubMed1987

On the mechanism of mitotic segregation induction in Aspergillus nidulans by benzene hydroxy metabolites.

The principal hydroxy-metabolites of benzene--hydroquinone, catechol and phenol--were assayed in tests for mitotic segregation induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most effective chemical, increasing the frequency of mitotic segregants up to 10-fold at 1-3 mM. Catechol was similarly active at 10-20 mM and phenol was weakly positive at 15 mM. Genetic characterization of induced abnormal segregating colonies by replating and complementary assays with haploid strain 35 suggest that gross chromosomal aberrations, instead of numerical abnormalities, are the primary genetic damages induced by hydroxybenzenes in A. nidulans. The protecting activity exerted by L-cysteine against equimolar concentrations of hydroquinone supports a free radical mechanism for hydroxybenzenes genotoxicity in A. nidulans.

Aspergillus nidulans↗
PubMed1987

Chemical and physical agents assayed in tests for mitotic intergenic and intragenic recombination in Aspergillus nidulans diploid strains.

Data from Aspergillus nidulans mitotic recombination assays published over the period 1960-1986 are briefly reviewed. The results of the testing of 104 chemical agents and three physical agents are summarized. A tentative comparison of the performance of recombinational, mutational and aneuploidy assays in A. nidulans suggests that the former can effectively detect DNA-damaging agents which either induce true genetic recombination (intergenic or intragenic crossing-over) or mimic it by inducing chromosome structural damage which allows the expression of recessive genetic markers. On the other hand, aneuploidy tests proved to be sensitive both to chemicals directly affecting chromosome segregation (e.g. spindle poisons) and to the majority of DNA-reactive compounds assayed.

Aspergillus nidulans↗