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Biomedical subjects

S Parodi

Publications and source records attributed to S Parodi.

At least 127 records · Page 7Linked to original sources
PubMed1989

Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.

The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes, 14C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment.

Animals↗
PubMed1989

Ultrasound examination in ovarian cancer patients. A comparison with second look laparotomy.

A series of 129 patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer, were evaluated with ultrasound examination and second look surgery. Results of both modalities were correlated in order to assess the reliability of ultrasound in detecting residual disease. After six cycles of chemotherapy, ultrasound was negative in 94 patients and positive in 35 patients. At second look, 57 patients were in complete pathologic remission, 16 had microscopic residual disease, 23 had macroscopic disease less than 2 cm, and 33 had macroscopic disease greater than 2 cm. Correlating ultrasonography and laparotomy, high correlations were seen in patients with no residual disease (92.2%); on the other hand, ultrasound examinations exhibited poor sensitivity and specificity in patients with microscopic disease (6.2%) and residual disease less than 2 cm (8.6%). Using ultrasound discrimination among patients with no residual disease, microscopic disease, or macroscopic disease less than 2 cm does not appear possible. Our suggestion is that ultrasound is not able to replace second look laparotomy in the detection of minimal residual disease in ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Biochemical and enzymatic aspects of caffeine and caffeine derivatives induced DNA strand breaks.

The results presented here point to the difficulties that exist in connection with the identification of the molecular target of caffeine. Our data support the evidence that caffeine and caffeine derivatives cause DNA-protein cross-links (DPC) in whole mammalian cells or in isolated nuclei. These DPC have the same properties (saturability, reversibility and temperature-dependence) as those produced by an enzymatic inhibition. The experiments performed in reconstituted systems, in the presence of purified DNA topoisomerase II, do not support the original hypothesis that this enzyme might be a possible target for this class of drugs. We suggest the possibility that other DNA metabolism enzymes are involved in the biological effects of caffeine and caffeine derivatives. Further biochemical and molecular data are necessary to identify which of these enzymes is in fact affected.

Animals↗
PubMed1989

DNA damage induced by some bile acids, evaluated with alkaline elution technique.

Bile acids are promoting agents in colon carcinogenesis. In this work we have tried to characterize the DNA alteration induced by bile acids in Sprague-Dawley male rats. Confirming previous findings, a clear increase in elution rate was observed at alkaline pH. No effect could be observed when the nuclei were washed before the elution, in condition totally unsuitable for the repair of the type of DNA damage induced by typical genotoxic agents. We advanced the hypothesis that the increased alkaline elution rate observed with bile acids could be independent of DNA fragmentation and related to changes in chromatin structure.

Animals↗
PubMed1989

Growth of cells from esophageal squamous cell carcinoma biopsies in a reconstituted basement membrane.

Cells from esophageal carcinoma biopsies were cultured on or inside a three-dimensional basement membrane matrix (matrigel). Their growth was compared to cells derived from control esophageal biopsies. Cells from both normal and neoplastic tissue attached poorly to tissue culture plastic. Matrigel coating improved adhesion and growth. When cells were grown inside a matrigel matrix, a striking difference was noticed between carcinoma cells and controls. Carcinoma cells grew invasively in the three-dimensional substrate and digested the matrix after a few weeks; control cells did not grow and only a few necrotic cells were visible with time. Matrigel provided a better growth substrate than plastic for esophageal derived cells and discriminated between carcinoma-derived and control cells when used as a three-dimensional growth substrate. Our studies suggest a possible use of matrigel for the selective growth of tumor cells derived directly from tissue biopsies.

Basement Membrane↗
PubMed1988

High chemotactic motility and growth in hard agar of a variant of RSV-transformed fibroblasts are lost in late passages.

Cloning efficiency in hard agar (0.6%) and high chemotactic migration toward fibroblast conditioned medium have been shown to characterize metastatic tumor cells. We studied growth in 0.6% agar and chemotaxis of two lines of Rous Sarcoma virus-transformed Balb/c3T3 cells, B77/3T3 (low metastatic) and AA12 (high metastatic), and compared them to their non-transformed counterpart, in order to verify whether these properties were maintained during several subcultivations. Cells were cryopreserved at early passages and thawed for experiments. Both assays were performed on freshly thawed cells (4-6 weeks in culture) and on cells which had been cultured 15-20 weeks after thawing. B77/3T3, which are tumorigenic but low metastatic and which have a very low cloning efficiency in hard agar (0.1-1%), showed a chemotactic response to Balb/c3T3 conditioned medium about two-fold higher than control Balb/c3T3. This response did not change with time in culture. AA12 cells, a genetic unstable variant of B77/3T3 selected for its growth in hard agar (0.6%), had a high cloning efficiency in hard agar and showed a high chemotactic motility (three-fold the controls). High growth in 0.6% agar and high chemotaxis of AA12 were lost in late passages, where cells behaved as the controls. It seems that besides the already reported variation in anchorage-independent growth, genetically unstable tumor cells can also have important variations in chemotactic motility during subcultivations.

Agar↗
PubMed1987

Characterization of the effects induced on DNA in mouse and hamster cells by lithocholic acid.

Lithocholic acid (LCA) is a promoting agent in colon carcinogenesis. In this work we have tried to characterize the DNA alteration induced by LCA in cells grown in vitro and in nuclei. Confirming previous findings, a clear increase in elution rate was observed at both alkaline and neutral pH. The extent of the increase was very similar at the two pHs. However, an increased elution rate could be observed only when lysing the nuclei at high ionic strength and low detergent concentration (2 M NaCl + 0.2% N-lauroylsarcosine sodium salt). No effect could be observed when the nuclei were lysed with a high detergent concentration (2% sodium dodecyl sulfate). In addition, a slight effect could be observed using a method for the evaluation of DNA unwinding in alkali. After termination of the incubation with LCA, the DNA alteration observed with DNA elution disappeared very rapidly both in intact cells and nuclei, even when the incubation buffer was totally unsuitable for the repair of the type of DNA damage induced by typical genotoxic agents. The effect of LCA on DNA was apparently not mediated through an inhibition of topoisomerase II. Only the intact chromatin of nuclei was responsive, not the quasinaked DNA of nuclei lysed at high ionic strength. We advance the hypothesis that the increased alkaline and neutral elution rate observed with LCA could be independent of DNA fragmentation and related to changes in chromatin structure.

Animals↗
PubMed1987

Possible implications from results of animal studies in human risk estimations for benzene: nonlinear dose-response relationship due to saturation of metabolism.

To date, all risk assessment studies on benzene have been based almost exclusively on epidemiological data. We have attempted a more integrated and quantitative evaluation of carcinogenic risk for humans, trying to utilize, in addition to the epidemiological data, all data available, specifically data on metabolism, genotoxicity, and carcinogenicity in small rodents. An integrated evaluation of the globality of the available data seems to suggest a progressive saturation of metabolic capacity both for man and rodents between 10 and 100 ppm. The most susceptible target cells seem to be different in humans (predominant induction of myelogenous leukemia) and small rodents (induction of a wide variety of tumors). Nevertheless, both epidemiological and experimental carcinogenicity data tend to indicate a flattening of the response for the highest dosages, again suggesting a general saturation of mechanisms of metabolic activation, extended to different target tissues. From a quantitative point of view, the data suggest a carcinogenic potency at 10 ppm two to three times higher than that computable by a linear extrapolation from data in the 100 ppm range. These observations are in accord with the recent proposal of the European Economic Community of reducing benzene time-weighted average occupational levels from 10 to 5 ppm.

Animals↗
PubMed1987

Chemotaxis of 3T3 and SV3T3 cells to fibronectin is mediated through the cell-attachment site in fibronectin and a fibronectin cell surface receptor.

Fibronectin (FN) is a multidomain extracellular matrix protein that induces attachment and chemotactic migration of fibroblastic cells. In this study we analyzed the molecular determinants involved in the FN-induced chemotactic migration of normal and SV40-transformed 3T3 cells. Two different monoclonal antibodies to the cell-binding site of FN blocked chemotaxis to a 140-kD FN fragment (Ca 140) containing the cell-binding domain. A monoclonal antibody to a determinant distant from the cell-binding site did not affect chemotaxis. A synthetic tetrapeptide, RGDS, which represents the major cell-attachment sequence, was able to compete with FN and the Ca 140 fragment in chemotaxis assays, but this peptide itself had no significant chemotactic activity. A larger peptide encompassing this sequence, GRGDSP, was chemotactic, while the peptide GRGESP, where a glutamic acid residue was substituted for aspartic acid, was inactive. Chemotactic migration could be prevented in a dose-dependent manner by a rabbit polyclonal antiserum to a 140-kD cell surface FN receptor. This antibody was more effective on normal than on transformed 3T3 cells. Neither the anti-FN receptor antiserum nor a monoclonal antibody to the cell-binding site of FN blocked migration induced by another potent chemoattractant, platelet-derived growth factor. These data indicate that FN-induced chemotaxis of 3T3 and SV3T3 cells is mediated via the RGDS cell-attachment site of FN and the 140-kD cell surface FN receptor. The interaction is specific and can be altered by transformation.

Animals↗
PubMed1987

Utilization of the quantitative component of the information obtained from short term tests.

We are referring in this paper to traditional tests of genotoxicity that are essentially detecting properties correlated with the initiating activity of chemical and physical agents. In classical initiation-promotion experiments, promotion is changing dramatically tumor frequency, but a better correlation between initiation and tumor frequency may exist when carcinogenesis experiments in rodents utilize only an initiator agent. End points, metabolism and target organs of short term test may be not optimal in respect to the real initiation process. In conclusion, we have to expect a very high level of statistical noise in the correlation between short term tests and carcinogenicity in rodents. Correlations of this type are not unique in science. For instance, the input data for weather forecasting and the real weather are often related with a high level of statistical noise. But this is not considered a good reason for throwing away the quantitative component of the input information. Similarly, in this context the utilization of the quantitative component of the information improves in a moderate, but not negligible way the predictive value of the information offered from short term tests, especially when they are used in a battery. In this review we discuss the possibility that, when studying correlations between genotoxicity tests and carcinogenicity in rodents, a quantitative approach could replace with important advantages the qualitative approach generally adopted up to the present time. The qualitative approach appeared as a more modest but realistic approach to the complexities of these correlation studies. What we suggest is that a quantitative approach mathematically not less correct than the qualitative approach is feasible. More precise and useful information for risk assessment evaluations can be obtained.

Animals↗
PubMed1987

The complementary role of primary prevention, early detection, and therapy in our fight against cancer.

Public health strategies for cancer control are determined by the epidemiological, clinical and biological characteristic of each cancer. Primary prevention is most easily implemented in cancers due to one or few factors. Secondary prevention is best suited for frequent cancers with a long preclinical, detectable phase. Therapy has to be relied upon in rare cancers of unknown etiology. A critical evaluation of the accomplishments of these three approaches shows that the potential role in cancer control of early detection and treatment is severely hampered by the high social and human costs, that are only partially counterbalanced by the limited effectiveness. As a consequence, primary prevention should be regarded as the key approach to cancer control, and efforts should be concentrated on studies concerning cancer etiology and on the implementation of preventive measures.

Female↗
PubMed1986

A simple model for DNA elution from filters.

DNA chain scission, induced both in vitro and in vivo by various agents, is an event of great biological relevance. The damage is currently evaluated by empirical membrane separation techniques; the results are quite reproducible and the sensitivity higher than 1 single strand break per 10(9) Daltons. We outline a simple theory of the filtration of coiled macrosolutes, having a random size distribution, through porous membranes, considered as being in quasi-steady flow. The basic transport equation Jj = cj (1 - sigma)Jv is solved by considering that the value of sigma j, the reflection coefficient of component j, (1 less than or equal to j less than or equal to N), is given by (1 - KjRj), where Kj is the partition constant between pore and solution, a function of the conformational entropy loss of the coil, and Rj accounts for the frictional force experienced by a particle moving along the pore. The problem of evaluating the volume Vs filled up with solute has been approached according to a simplified theory of the excluded volume for flexible polymers; the result is Vs = sigma nj4/3 pi(rGj)3 where rGj is the jth radius of gyration. The solution of the resulting set of N differential equations gives nj, the number of molecules of component j remaining on the filter, as a function of the elution volume V. The theory demonstrates that the process is governed by the average dimensions of the coil, so affording a universal calibration of filter elution methods, in excellent agreement with the experiments.

Animals↗
PubMed1986

A choline-devoid diet, carcinogenic in the rat, induces DNA damage and repair.

A diet deficient in choline when fed to rats for as few as 3 days resulted in liver DNA damage. The damage could be monitored as alkali-labile lesions using alkaline-sucrose gradients as well as alkaline elution technique. The DNA damage disappeared when the choline-deficient diet was replaced by a choline-supplemented diet suggesting the alkali-labile lesions were repairable. The DNA damage was detected at a time when no liver cell death was detectable. The induction of DNA damage in a proliferating liver by the choline-deficient diet may be an early important event leading to initiation of liver carcinogenesis.

Animals↗