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R Zito

Publications and source records attributed to R Zito.

43 records · Page 3Linked to original sources
PubMedDate not supplied

Divergent synergic effects in carcinogenesis initiation by simultaneous exposure to two genotoxic carcinogens.

Carcinogenesis is a complex and multistep process starting from initiation to tumor progression. Synergistic mechanisms can occur at every step of the process. The aim of this work was to provide information about the effect of chemical carcinogens which, if administered in combination, result in positive as well as negative synergistic effects. In order to evaluate whether for some carcinogens synergism occurs at the initiation step, we compared the effects of Ethylmethanesulfonate (EMS) on Benzo[a]pyrene (BP)-DNA adducts formation in the liver and lung of male Swiss mice treated for seven days by i.p. dose of EMS (1.2 mg/Kg b.w.) alone or by simultaneous administration of three doses of BP (25, 50, 100 mg/Kg b.w.) injected i.p. or the first day of treatment. A group of Swiss mice was treated by BP alone. At it was demonstrated in our laboratory that previous immunization toward BP influences the adduct levels of this carcinogen (14), the same treatments (BaP alone and BaP with EMS) were carried out in mice previously immunized toward BP. Liver and lung 1 BP-DNA adducts were detected in all the groups treated by both BP and EMS as compared to the group treated with BP alone. The EMS-BP association in non-immunized mice showed an antagonistic effect in the liver and a synergistic effect in the lung. In immunized mice a synergistic effect was obtained in both liver and lung. Moreover, the efficiency of both the synergistic and antagonistic effect, depended on BP dose of treatment. It is reasonable to draw the conclusion that simultaneous exposure to BP and EMS leads to different organ-specific and dose-dependent effects. This first preliminary result showed that the pattern of the interaction between genotoxic carcinogens is more complex that was foreseen, even at the stage of DNA adducts formation.

Animals↗
PubMedDate not supplied

Specificity of rabbit antibodies elicited by related synthetic peptides.

Three 17-residue peptides, presenting from 65% to 70% sequence homology, and one endecapeptide, with no apparent homology with the first three, were chemically synthesized and investigated in their ability to elicit rabbit antipeptide antibodies. The complex cross reactivities of the antisera were investigated by testing the binding of the antibodies to the intact peptides, to their enzymatic fragments, and by the use of specific immunoadsorbents. Antipeptide antibodies may or may not crossreact with related "parent" peptides, this depending upon number, distribution, and localization of amino acid differences in low or high antigenicity regions of the immunogen. Related peptides may elicit antibodies that crossreact almost completely, and therefore not specific for one or the other "parent" peptide. Those antibodies may therefore be of little use for the selective recognition of closely related structures.

Amino Acid Sequence↗
PubMedDate not supplied

Determination of serum levels of 2,6 diethylaniline in laboratory animal treated with Alachlor.

In order to estimate the environmental risk of the use of Alachlor, experiments on laboratory animals were conducted. Alachlor and 2,6 diethylaniline content in blood serum was quantified. Three groups of male ACI/T rats and C3H/FEJ mice were treated with three different doses of Alachlor. Six hours after the intraperitoneal injection the animals were bled and blood was collected by cardiac puncture. From serum obtained after blood centrifugation, A and DEA were extracted using diethyl ether. 2,6 diethylaniline and Alachlor determinations were carried out by high performance liquid chromatography (HPLC). The HPLC revealed that the metabolic capacity of 2,6 diethylaniline production from Alachlor in rats is dose-dependent; moreover, the animals can be subdivided into at least two groups, according to their Alachlor metabolic capacities. In mice the metabolic release of 2,6 diethylaniline was found to be practically complete at every dose tested.

Acetamides↗
PubMedDate not supplied

Identification of optimal conditions for the detection of benzo[a]pyrene-DNA adducts by enzyme-linked immunoadsorbent assays (ELISA).

The aim of the present report was to establish the optimal conditions for the detection of polycyclic aromatic hydrocarbon adducted to DNA by enzyme-linked immunoadsorbent assays (ELISA). Racemic 7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene ((+/-)-anti-BPDE) modified DNA samples were produced in vitro, by reacting (+/-)-anti-BPDE with calf thymus DNA, and in vivo in Swiss female mice by single i.p. injection of benzo[a]pyrene (B[a]P) (200 mg/kg body weight dissolved in tricaprylin). The BPDE adduct content in vitro and in liver and lung modified DNA was detected by direct and competitive ELISA using serial dilutions of the samples in unmodified calf thymus DNA, and polyclonal rabbit immunoglobulin-G elicited toward BPDE-DNA and BPDE-gelatin, both produced in our laboratory. The carcinogen-macromolecule conjugate in which adducts were sought could be used as an immunogen to produce a specific and potent antibody. Moreover, the modification level of the ELISA standards should be as close to the range as of the biological samples to correctly calculate the adducts, since different binding efficiency between antibody and BPDE-modified DNA is dependent on the BPDE modification level (33). Appropriate extraction of the in vitro modified samples is also necessary to guarantee the exact covalent modification level, eliminating noncovalently linked BPDE. Under these conditions, our results confirm that competitive ELISA is much more sensitive than the direct method, mainly because of the limitations caused by the coating of the antigen in each well (max 5 micrograms DNA/well), whereas the amount of DNA (modified or not) that can be employed for adduct detection by competitive ELISA increases 20-fold. The sensitivity obtained was 0.5 fmol B[a]P/microgramDNA (1.6 adducts/10(7) nucleotides).

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗