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C Della Croce

Publications and source records attributed to C Della Croce.

14 recordsLinked to original sources
PubMed2004

Genetic and metabolic effects of gluconasturtiin, a glucosinolate derived from cruciferae.

It is thought that induction of detoxifying phase-II drug metabolizing enzymes or inhibition of bioactivating phase-I by phytoalexins could protect against mutagens and neoplasia. In the search for potential naturally occurring molecular chemoprevention agents, particular attention has been devoted to isothiocyanates, which are breakdown products-via myrosinase-of glucosinolates such as gluconasturtiin (GNST), a natural constituent of cruciferae. Here, we first investigated the ability of GNST to modulate metabolizing enzymes in male Swiss Albino CD1 mice injected by gavage (24 mg/kg or 48 mg/kg b.w.) with GNST either in single or repeated (daily for four consecutive days) dose. Using selected probes to various cytochrome P450 (CYP) isoforms, a marked and generalized decrease of CYP content, NADPH-(CYP)-c-reductase and various CYP-linked monooxygenases (measuring CYP1A1, CYP2B1/2, CYP3A1/2, CYP1A2 and CYP2E1), was observed in hepatic, renal and pulmonary subcellular preparations (up to approximately 66% loss, liver). Similar behavior was recorded using the regio- and stereo-selective hydroxylation of testosterone as multibiomarker (CYP2A1 and CYP2B9, up to approximately 96% loss), as well as with the phase-II marker glutathione S-transferase (up to approximately 50% loss, liver). We also performed genotoxicity investigations, using the diploid D7 strain of yeast Saccharomyces cerevisiae as a biological test system. GNST was able to significantly induce point reverse mutation in growing cells without myrosinase, thus suggesting either a direct GNST or a CYP-linked metabolite role in the genotoxic response. On the contrary, in suspension test, the addition of myrosinase significantly increased mitotic gene conversion, probably due to the formation of GNST-derived phenylethyl isothiocyanate (PEITC) breakdown product. Taken together, our data suggest that GNST exerts a dual effect: while strongly inhibiting the microsomal (bioactivating) metabolism, GNST also possesses genotoxic activity. This concomitant mutagenic activity underlines the necessity of overall toxicological characterization of this (or any other molecule) prior to mass chemopreventive use.

Animals↗
PubMed2000

Genotoxic and mono-oxygenase system effects of the fungicide maneb.

The in vivo effects of a commercial preparation of maneb on mono-oxygenase activities of hepatic microsomes of basal and induced rats were examined. In vitro experiments with the D7 strain of yeast Saccharomyces cerevisiae were also performed. In both basal and induced rats maneb caused a decrease in cytochrome P-450 content and aniline hydroxylase. Immunoblotting analysis using anti-P-450 IIE1 antibodies confirmed the data obtained for aniline hydroxylase activity. Maneb was toxic in cells of S. cerevisiae. On the basis of in vivo and in vitro experiments it can be concluded that maneb possesses a toxic activity attributable to its main metabolite ethylene thiourea. Immunoblotting analysis indicates that maneb biotransformation influences the IIEI P-450 isoform.

Aniline Hydroxylase↗
PubMed1998

Isolation of a novel metabolizing system enriched in phase-II enzymes for short-term genotoxicity bioassays.

Murine S9 liver fractions isolated from mice fed 7.5 g kg-1 2(3)-tert-Butyl-4-hydroxyanisole (BHA) for 3 weeks were tested to determine: (a) the profile of both phase-I and phase-II xenobiotic metabolizing enzymes; (b) their ability to induce in vitro covalent binding of some precarcinogens to calf thymus DNA; and (c) their activation in a standard genetic toxicology assay. With regard to phase-I pathway, the S9 fraction expressed various cytochrome P-450-(CYP) (classes 1A1, 1A2, 2B1, 2E1, and 3A)-dependent biotransformation enzymes at levels comparable with those present in murine control liver. For post-oxidative enzymes, the S9 expressed high levels of glutathione S-transferases (up to 12-fold increase), glutathione S-epoxide-transferase (up to 2.6-fold), UDP-glucuronosyl transferase (up to 5.3-fold) and epoxide hydrolase (up to 2.6-fold) activities, as compared to untreated mice. The in vitro DNA binding of the precarcinogenic agents [14C]-1,4-dichlorobenzene, [14C]-1,2-dichlorobenzene and [14C]-1,4-dibromobenzene, mediated by BHA-induced cytosol and/or microsomal preparation, showed an increase in specific activity comparable to that observed with phase-I (PB/beta NF) induced S9. In some instances, covalent binding was even more elevated using the BHA-induced systems as compared with traditional S9 fractions. For example, cytosol derived from BHA-administered mice was able to induce a significant binding to calf thymus DNA up to 26.2-fold increase for [14C]-1,4-dichlorobenzene, while cytosol from PB/beta NF was not. A high mutagenic response on diploid D7 strain of Saccharomyces cerevisiae as exemplified by a marked induction of mitotic gene conversion and point (reverse) mutation confirmed that BHA-derived S9 fractions activate precarcinogens to final genotoxins. Because a number of chemicals are activated by either oxidative or post-oxidative enzymes, the use of metabolizing biosystems, with an enhanced phase-II pathway, together with classical S9 fractions, can improve the sensitivity of the assay in detecting unknown genotoxins.

Animals↗
PubMed1996

Biochemical and genetic interactions of two commercial pesticides with the monooxygenase system and chlorophyllin.

Two commercial preparations of atrazine and zineb were tested on a diploid D7 strain of the yeast Saccharomyces cerevisiae using cells from logarithmic growth phase (with a high level of cytochrome P-450) and from stationary growth phase. The compounds induced marked increases of both gene conversion and point mutation frequencies in the logarithmic phase cells, while in the stationary phase no genotoxic effect was observed. The results obtained employing TA98 and TA100 strains of Salmonella typhimurium (Ames test) confirmed that neither atrazine nor zineb were mutagenic. The interaction between zineb and chlorophyllin, a known antimutagen in several biological systems, has been evaluated in yeast cells from logarithmic growth phase. The results showed that chlorophyllin seems to have a protective role against the genotoxic effects of zineb. The in vivo effects on cytochrome P-450 content (Cyt. P-450) and on monooxygenase activities were examined in hepatic microsomes of induced animals (rat, pig, and rabbit) 24 hrs after acute treatment. The results obtained with atrazine showed that it caused different effects in the three animal species. Preliminary data with zineb indicated that it can act both as an inducer or as an inhibitor of the monooxygenase system, depending on the dose used.

Animals↗
PubMed1996

Antimutagenesis and anticancer effects.

Cancer development is a multistage process wherein mutational events play an important role. Various antimutagen components, in particular magnesium and selenium, have been reported to have anticarcinogenic properties. These two oligoelements display different behaviors according to their concentrations. The different effects of magnesium and selenium depend on the different mechanisms of cell absorption. The importance of antimutagenesis studies in cancer prevention is reported and a review of the basic mechanisms operative in antimutagenesis, including some data on known antimutagens, is made.

Animals↗
PubMed1995

Effect of magnetic fields on rodent monooxygenase enzymes.

The effects of 50 Hz, 1.2 mT magnetic fields (MFs) were tested on hepatic monooxygenase enzymes of basal and beta-naphthoflavone-phenobarbital-preinduced rats and mice. An inductive effect on cytochrome P-450 level and on some enzymatic cytochrome P-450-dependent activities was observed in basal mice after MF exposure. Enzymatic activities in preinduced mice and rats were reduced by MFs, the degree of reduction depending on the enzyme. A specific inhibitory effect was determined in some of the assayed activities and in the relative peculiar P-450 isoforms detected by Western blot analysis.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1995

Magnesium: its role in cellular functions--a review.

Magnesium has been identified as an important element in cellular functions, and its abnormalities have far-reaching effects in pathology. We reviewed its effects in the cell cycle, its physiological role, nutritional aspects, toxicity, mutagenesis, and tumorigenesis.

Anticarcinogenic Agents↗
PubMed1992

Antimutagenicity in yeast.

In recent years there has been increasing interest in antimutagenesis, and studies have been done using both prokaryotic and eukaryotic systems. In eukaryotic systems the first studies were performed with different strains of Schizosaccharomyces pombe. In particular, caffeine and L-methionine were investigated. Different strains of Saccharomyces cerevisiae were employed in studies of a wide variety of compounds, including acridine, saccharin, salts, tumor promoters and co-carcinogens. Strain D7 was widely employed and antimutagenic activity of spermine, chlorophyllin, cobaltous chloride and fermented milk is reported.

Animals↗
PubMed1992

Influence of cinnamaldehyde on UV-induced gene conversion and point mutation in yeast: effect on protein synthesis.

The activity of cinnamaldehyde (CIN), a bioantimutagen in bacterial systems, was tested in the D7 strain of yeast Saccharomyces cerevisiae. Yeast cells were UV-irradiated and post-incubated in liquid growth medium for 2 and 4 h with different concentrations of cinnamaldehyde. During the post-incubation period, DNA-damage-specific functions may be induced. This in turn may affect the genotoxicity and in fact a weak decrease in UV-induced convertant and revertant frequencies was observed after 4 h of post-incubation. The presence of CIN in the growth medium increased the UV-induced gene conversion and reversion. The addition of cycloheximide abolished this effect. To evaluate the CIN effect on protein synthesis, extracts of cells UV-treated and post-incubated for 2 h in the presence of 35S-methionine were performed. SDS-gel electrophoresis demonstrated the inhibitory effect of CIN on a UV-specific protein. This work suggests that CIN might interfere with DNA-damage-inducible systems although it did not exert an antimutagenic activity in our experimental conditions.

Acrolein↗
PubMed1991

Genotoxicity of vanadium compounds in yeast and cultured mammalian cells.

The ability of vanadium compounds to induce genetic activity was investigated in D7 and D61M strains of Saccharomyces cerevisiae and in Chinese hamster V79 cell line. In our previous work, ammonium metavanadate (pentavalent form, V5) induced mitotic gene conversion and point reverse mutation in the D7 strain of yeast. The genotoxicity was reduced by the presence of S9 fraction, which probably reduced pentavalent vanadium to the tetravalent form. In the present study, vanadyl sulfate (tetravalent form, V4) induced no convertants and revertants in yeast cells harvested from stationary growth phase. With yeast cells from logarithmic growth phase, which contain high levels of cytochrome P-450, a significant increase in genetic effects was observed. Further experiments, performed by treating cells harvested from logarithmic growth phase in the presence of cytochrome P-450 inhibitors, indicated that the monooxygenase system influenced the genotoxicity of metavanadate while the genetic activity of vanadyl remained unaffected. Aneuploidy effect in the D61M strain of Saccharomyces cerevisiae was induced by either V5 or V4, confirming that vanadium compounds are potentially antitubulin agents in eukaryotic cells. Although these compounds are very toxic in V79 cells, no mutagenic effect was observed in the presence or in the absence of S9 fraction.

Animals↗
PubMed1990

Vanadium: genetical and biochemical investigations.

Ammonium metavanadate was studied for its ability to induce mitotic gene conversion and reverse point mutation in the D7 strain of Saccharomyces cerevisiae. Metavanadate increased the convertant and revertant frequencies; the highest activity was observed without metabolic activation. This indicated that the S9 hepatic fraction and yeast cells in logarithmic phase (and containing a high level of cytochrome P450) biotransform vanadate, probably reducing it to vanadyl. In addition, the effect of ammonium metavanadate on the hepatic monooxygenase system was studied in mice by measuring the level of cytochrome P450 and determining the activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and 7-ethoxycoumarin O-deethylase in mouse liver microsomal fraction. The results indicated that this compound reduced mono-oxygenase activity and also the level of cytochrome P450.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

Protective effect of lipoic acid against hydrogen peroxide in yeast cells.

Lipoic acid (LA) is found in all kinds of cells, it is widely used in medicine and as a dietary supplement, and it is involved in different physiological functions. Even if there are many papers regarding therapeutic effects of LA, medical research does not always support its effectiveness and little is known about LA metabolism in eukaryotic cells. In this work the probable protective effect of LA was investigated employing five strains of yeast Saccharomyces cerevisiae through short term assays. In particular LA behaviour in oxidative stress conditions was studied. For this purpose hydrogen peroxide was used as oxidant. In D7 strain, LA showed antimutagenic effects against hydrogen peroxide and decreased significantly cytochrome P450. To better elucidate the effect of LA the following yeast strains carrying deletions in superoxide dismutase genes (SOD) were employed: EG-103 (wild type), EG-110 strain (without mytochondrial SOD), EG-118 (without cytoplasmatic SOD) and EG-133 (without both enzymes). LA increased the number of mitotic divisions in EG-103, EG-110 and EG-133 and in growing cells (EG-103, EG-110, EG-118) it increased survival percentage with respect to hydrogen peroxide. The positive action was evident in D7 and in EG strains and it showed that LA can be protective and antimutagenic against oxidants in yeast cells, via its antioxidant activity.

Antimutagenic Agents↗