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P Perocco

Publications and source records attributed to P Perocco.

At least 37 records · Page 2Linked to original sources
PubMed1993

In vitro cytotoxic and cell transforming activities exerted by the pesticides cyanazine, dithianon, diflubenzuron, procymidone, and vinclozolin on BALB/c 3T3 cells.

Cytotoxic and cell transforming activities of the pesticides cyanazine, diflubenzuron, dithianon, procymidone, and vinclozolin were investigated in vitro by utilizing the BALB/c 3T3 cell transformation test performed in the presence or in the absence of S-9 mix as an exogenous bioactivation system for the chemicals. All the assayed pesticides were cytotoxic in the absence of S-9 mix, whereas only dithianon exerted cytotoxic effects in the presence of metabolic activation. All the chemicals tested did induce BALB/c 3T3 cell transformation, to a various extent, in the absence of S-9 mix. Cell transforming ability of cyanazine and diflubenzuron was not detectable in the presence of S-9.

3T3 Cells↗
PubMed1993

Induction of chemotactic and invasive phenotype in BALB/c 3T3 cells by 1,2-dibromoethane transformation.

1,2-Dibromoethane (DBE), which can act as initiating agent, is capable of inducing a malignant phenotype in BALB/c 3T3 cells. Cells transformed with a single noncytotoxic dose formed more progressive tumors in vivo. Almost all animals (95%) receiving the inoculum of two different transformed clones developed tumors within 1 month. In the control group only 55% of the animals developed tumors after 4 months. Treatment with DBE also increased the chemotactic properties of target cells, which also acquired ability to penetrate and colonize a reconstituted basal membrane (matrigel). These data suggest that DBE could play a key role in tumor progression.

3T3 Cells↗
PubMed1993

In vitro cell transformation induced by the pesticide fenarimol.

The pesticide fenarimol is capable of transforming BALB/c 3T3 cells in an in vitro model system, and its action resembles a carcinogenic process in vivo. In the absence of metabolic activation, transformed foci are already visible in the standard experimental procedure. The addition of the S9 fraction as an exogenous metabolic system leads to a decrement of cytotoxic effects and the reduction of the transformation rate. The transformed phenotype, however, becomes visible when confluent cells are replated and allowed further cell replication. Transformation effects by fenarimol may be due to both a weak genotoxic activity and/or stronger promoting activity.

Animals↗
PubMed1992

Initiating activity of 1,1,2,2-tetrachloroethane in two-stage BALB/c 3T3 cell transformation.

By using in vitro two-stage BALB/c 3T3 cell transformation assay, we have tested the effect of promoting treatment with tetradecanoylphorbol acetate (TPA) on transformation induced by 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE). Cells were treated with subeffective or transforming concentrations of 1,1,2,2-TTCE in the presence of an S9-mix activating system, followed by TPA promoting treatment. The transforming activity of 1,1,2,2-TTCE is evident only by reseeding confluent cells and allowing additional rounds of cell replications in the amplification test. Treatment with TPA leads to a marked transformation yield in all plates scored even at the lowest assayed dosage of 1,1,2,2-TTCE, without performing amplification of transformation.

3T3 Cells↗
PubMed1991

Chloroform bioactivation leading to nucleic acids binding.

Chloroform was bound covalently to DNA, RNA and proteins of rat and mouse organs in vivo after i.p. injection. Covalent Binding Index values of rat and mouse liver DNA classify chloroform as a weak initiator. Labelings of RNA and proteins from various organs of both species were higher than that of DNA. In an in vitro cell-free system, chloroform was bioactivated by cytochrome P450-dependent microsomal fractions, by cytosolic GSH-transferases from rat and mouse liver, and particularly by the latter enzymes from mouse lung. This observation suggests that GSH plays a role in the binding of chloroform metabolites to DNA. The presence of both microsomal and cytosolic enzymatic systems in the standard incubation mixture generally led to an additive or synergistic bioactivating effect for rat and mouse, respectively.

Animals↗
PubMed1991

Transforming activity of ethylene dibromide in BALB/c 3T3 cells.

Ethylene dibromide was capable of inducing in vitro transformation of BALB/c 3T3 cells either in the presence or in the absence of exogenous metabolic activation (S9-mix). This transforming effect was evidenced by the induction of a higher number of transformed foci as compared to the controls performed with untreated cells or solvent vehicle-treated cells. In the absence of exogenous activation, all assayed doses (ranging from 23.4 micrograms/ml to 187.9 micrograms/ml) exerted transforming activity. Number of foci obtained in EDB-treated plates antransformation frequency of the target cells were higher than those detected in the transformation test performed in the presence of S9-mix.

3T3 Cells↗
PubMed1990

Evaluation of genotoxic effects of the herbicide dicamba using in vivo and in vitro test systems.

The genotoxic effects of the herbicide dicamba have been studied by measuring 1) the unwinding rate of liver DNA from intraperitoneally (i.p.) treated rats (fluorimetric assay); 2) DNA repair as unscheduled DNA synthesis (UDS) induced in cultured human peripheral blood lymphocytes (HPBL); and 3) sister chromatid exchanges (SCE) in HPBL. Results show that dicamba is capable of inducing DNA damage since it significantly increases the unwinding rate of rat liver DNA in vivo and also induces UDS in HPBL in vitro in the presence of exogenous metabolic activation (S-9 mix). Furthermore, dicamba causes a very slight increase in SCE frequency in HPBL in vitro.

Animals↗
PubMed1990

GM-CSF incubation prior to treatment with cytarabine or doxorubicin enhances drug activity against AML cells in vitro: a model for leukemia chemotherapy.

We studied the effect of preincubation with recombinant GM-CSF on the activity of cytarabine and doxorubicin against clonogenic acute myeloid leukemia cells (CFU-AML). Leukemia cells from seven persons with AML, three myeloid cell lines (HL60, KG1, K562) and two control cell lines (U937, MOLT3) were tested. Preincubation with GM-CSF (0.01-0.1 microgram/ml) increased DNA synthesis as measured by tritiated thymidine incorporation and intranuclear Ki67 expression in cells from six persons with AML and in HL60 cells. Leukemia cells preincubated with GM-CSF for 6-48 h were exposed to cytarabine (2-200 micrograms/ml) or doxorubicin (0.01-0.1 microgram/ml) for 3 h and CFU-AML assayed. This approach further reduced CFU-AML in samples from six persons with AML and in HL60 and KG1 cells compared to cells not preincubated with GM-CSF prior to drug treatment. In most instances, reduced CFU-AML correlated with GM-CSF induced DNA synthesis. These data suggest a possible strategy of GM-CSF pretreatment to increase anti-leukemia efficacy of chemotherapy in AML.

Cytarabine↗
PubMed1990

The covalent interaction of 1,4-dibromobenzene with rat and mouse nucleic acids: in vivo and in vitro studies.

1,4-Dibromobenzene (1,4-DBB) was covalently bound to DNA from liver, kidney, lung and stomach of mice after intraperitoneal administration. The covalent binding index (CBI) value (23 in mouse liver) was typical of weak initiators. On the contrary, no interaction with DNA from rat organs was observed (CBI detection limit: 1.3-2.6). The in vitro interaction of 1,4-DBB with calf thymus DNA was mediated mainly by microsomes, especially those from liver of both species and from mouse lung. Mouse subcellular fractions were more active then rat subcellular fractions. Unlike liver cytosol, subcellular cytosolic fractions from lung, kidney and stomach were capable of bioactivating 1,4-DBB, although to a lesser extent than liver microsomes. Both cytochrome P-450 and GSH-transferases are involved in 1,4-DBB bioactivation.

Animals↗
PubMed1990

In vitro transformation of BALB/c 3T3 cells by 1,1,2,2-tetrachloroethane.

1,1,2,2-Tetrachloroethane (1,1,2,2-TTCE) was shown to be capable of inducing in vitro transformation of BALB/c 3T3 cells (clone A-31) either in the presence or in the absence of S9 activating system using an amplification-transformation (level-II) assay by reseeding confluent cells from each treatment and allowing additional rounds of cell replication. In the absence of metabolic activation, the highest assayed dose (1000 micrograms/ml), exerting the highest toxicity, was the only transforming dose. Lower doses of 1,1,2,2-TTCE were capable of transforming BALB/c cells in the presence of S9 activating system, the dose of 500 micrograms/ml exerting the highest transforming activity. The number and size of transformed foci recognized in the level-II plates were a function of the number of cells reseeded in the amplification assay. Foci obtained in the presence of S9 activating systems were larger in size, more deeply basophilic, and exhibited denser multilayering of constituent cells than foci recognized in the absence of exogenous metabolic activation.

Animals↗
PubMed1989

Toxic and DNA-damaging activities of the fungicides mancozeb and thiram (TMTD) on human lymphocytes in vitro.

The cytotoxic and mutagenic effects of the fungicides mancozeb and thiram were studied using human peripheral blood lymphocytes cultured in vitro with or without an S-9 mix microsomal metabolizing system. The results obtained suggested that the chemicals caused dose-dependent inhibition of thymidine uptake and unscheduled DNA synthesis on both resting and proliferating lymphocytes in the absence of the S-9 mix. In the presence of the S-9 mix, only thiram showed mutagenic activity by eliciting unscheduled DNA synthesis and a significantly higher frequency of sister chromatid exchanges than did controls.

Cell Survival↗
PubMed1985

Mutagenic and toxic effects of 4-hydroperoxycyclophosphamide and of 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557) on human lymphocytes cultured in vitro.

Certain biological effects exerted by 4-hydroperoxycyclophosphamide and by 2,4-tetrahydrocyclohexylamine (ASTA-Z-7557), utilized in vitro in the therapy of leukemias and lymphomas to eliminate the occult tumor cells in autologous marrow transplantations, were studied in human lymphocytes cultured in vitro. The data show that these drugs exert mutagenic activity eliciting unscheduled DNA synthesis (reparative synthesis) after DNA damage and cause about tenfold higher frequency of sister chromatid exchanges than controls. Furthermore, they exert strong toxic effects, measured as tritiated thymidine uptake inhibition, on mitogen-stimulated dividing cells even if pretreated during the nonproliferative phase of the cell cycle in which the toxic activity of the drugs is not detectable. Data obtained with doses of the drugs similar to those used in the therapy are discussed in terms of the therapeutic use of these chemicals.

Cell Survival↗
PubMed1983

Toxic, DNA-damaging and mutagenic activity of epichlorohydrin on human cells cultured in vitro.

Epichlorohydrin (ECHH) highly inhibited the tritiated thymidine uptake by human lymphocytes cultured in vitro, although the corresponding cell viability was unaffected. Furthermore, it elicited unscheduled DNA synthesis, acting as a DNA-damaging agent after its metabolic activation. ECHH also showed a clear toxic and mutagenic activity toward a human epithelial-like cell line, causing a decrease in cell viability and an increase in mutants resistant to 0.05 Lf/ml of diphtheria toxin.

Cell Line↗
PubMed1983

The immunomodulatory activity of the plant proteins Momordica charantia inhibitor and pokeweed antiviral protein.

The immunological activity of Momordica Charantia inhibitor (MCI) and of Pokeweed antiviral protein (PAP-S), 30,000 daltons plant proteins possessing close similarity to Ricin A chain as inhibitor of protein synthesis, was investigated in mice. In vivo, single nontoxic injections of microgram amount of these substances delayed H2-incompatible skin allograft rejection, splenocyte responsiveness to ConA and PHA, but not to LPS, and abrogated the PFC response to a T-dependent (SRBC) antigen while totally sparing that to a T-independent (S III) stimulus. Injection of these substances could also reduce NK cell activity while increasing macrophage-mediated spontaneous cytotoxicity. In vitro, MCI and PAP-S at non-cytotoxic concentrations inhibited lymphoid cell responsiveness to PHA and ConA, but not to LPS, and markedly enhanced macrophage-dependent cytotoxicity.

Animals↗
PubMed1983

Toxic activity of seventeen industrial solvents and halogenated compounds on human lymphocytes cultured in vitro.

Seventeen chemicals (solvents, insecticides and intermediates in the production of textiles and resins) were tested in a short-term in vitro system with human lymphocytes to determine their toxic action. The parameters studied were the tritiated thymidine uptake and cell viability in cultures grown with or without a rat liver metabolizing system (S-9 mix). Data obtained showed that 1,3-dichlorobenzene, 1,2-dichlorobenzene, hexane, 1,2-diiodoethane, 1,4-dichlorobenzene, tetrachloroethylene, 2,3-dibromopropanol, chloromethyl methyl ether, 1,2- and 1,3-dibromopropane, in order, exerted the more toxic effects; ethyl acetate, cyclohexane, cyclohexanone and benzene showed lower toxic activity. The chemicals lost their toxic power in the presence of the metabolizing system with the exception of 1,2- and 1,3-dichlorobenzene which maintained in some degree their toxicity even in the presence of the S-9 mix. Only chloromethyl methyl ether elicited unscheduled DNA synthesis acting as DNA damaging agent.

Adult↗
PubMed1982

Increase of sister chromatid exchange and unscheduled synthesis of deoxyribonucleic acid by acrylonitrile in human lymphocytes in vitro.

The investigation has been carried out on cultures grown in the presence of 5 x 10(-1) - 5 x 10(-5) M acrylonitrile with or without a rat liver metabolizing system (S-9 mix). The results obtained showed that acrylonitrile was toxic starting from the 5 x 10(-3) M concentration, caused a significant increase in the sister chromatid exchange (SCE) frequency in comparison with the controls (p less than or equal to 0.001) when the concentration was 5 x 10(-4) M, and elicited reparative deoxyribonucleic acid (DNA) synthesis, determined by tritiated thymidine uptake, particularly when the concentration was 5 x 10(-1) M. These effects were observed in lymphocytes of different donors and after drug activation by the S-9 mix metabolizing system.

Acrylonitrile↗
PubMed1981

DNA damage by haloalkanes in human lymphocytes cultured in vitro.

The DNA damaging activity of 7 haloalkanes was studied in a short-term in vitro system which utilized human lymphocytes. The parameters studied were the inhibition of scheduled (duplicative) and unscheduled (reparative) DNA syntheses seen as tritiated thymidine uptake. The results obtained suggested that chloromethyl methyl ether (CMME), 1,2-dibromoethane (DBE), trichloroethylene (TCE) and 1,2-dichloroethane (DCE) gave positive results such as DNA damaging agents, while carbon tetrachloride (CTC), chloroform (TCM) and dichloromethane (DCM) gave low or negative results.

Carbon Tetrachloride↗