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Biomedical subjects

P Perocco

Publications and source records attributed to P Perocco.

At least 19 recordsLinked to original sources
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↗
PubMed1977

Compared effects of N-hydroxyurethan, urethan and hydroxyurea on DNA synthesis. In vivo and in vitro studies.

The effect of N-hydroxyurethan (HUR) on DNA synthesis has been tested both in vivo on various tissues and in vitro on concanavalin A (ConA)-stimulated rat thymocytes and compared with the action of urethan and hydroxyurea. HUR suppresses scheduled DNA synthesis, except that of non-stimulated spleen cells in vitro. The inhibition is efficient and rapid and takes place immediately if the drug is administered at the peak of the S-phase. UR inhibits DNA synthesis in vitro only at much higher doses and with different time course. It is effective or slightly effective if it is administered at the peak of the S-phase. A conversion of urethan into HUR the latter depressing DNA synthesis could partly explain the differences observed. No toxicity was found after treatment with drugs at the concentration employed. Finally, the relationships between drug doses and cell responses have been particularly observed in vivo.

Animals↗
PubMed1976

Selective effect on T and B cell subpopulations in rat lymphoid organs after urethan treatment.

In vitro phytohemagglutinin (PHA) and concanavalin A (Con A) responsiveness of thymus and bone marrow cells, and E, EA, and EAC rosette-forming cells (E, EA, EAC) of these organs and spleen were studied in Fisher rats at various time intervals following a carcinogenic treatment with urethan (UR). Immediately after treatment, organ cellularities were drastically reduced with a progressive recovery as time passed. 1 day after treatment, the response of thymocytes to PHA showed a fourfold increase while organ cellularity dropped to 1%. This response fell below normal values after 7 days with an overshoot after days 14 and 21. UR-treated bone marrow cells showed a response to PHA below normal values after 1 and 7 days, a twofold increase after 3 days and an overshoot after 14 and 21 days. The responsiveness to Con A of both organs was affected by UR treatment to a much lesser extent, although following a pattern similar to that of PHA. E were never found, whether in normal nor in UR-treated animals. As far as the B-cell compartment is concerned, UR causes a progressive diminution of EAC, while the number of EA remains unaffected. The data are discussed in terms of selective effect on T- and B-cell subpopulations.

Animals↗