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S Parodi

Publications and source records attributed to S Parodi.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Utilization of the quantitative component of positive and negative results of short-term tests.

In this paper we discuss the possibility of utilizing not only the qualitative component of the information obtained from long-term and short-term tests (as is customary), but also the quantitative component of the results. We suggest that there is probably a precise mathematical relationship between the qualitative and quantitative approaches. We show that utilizing the quantitative approach, it is possible to give confidence limits to a given prediction, a possibility potentially very useful for risk evaluation. We show that starting from a reasonable working hypothesis, it is possible to include even negative data in a unified quantitative approach. Incorporating the quantitative component of the information could offer appreciable gains in predictivity, especially when utilizing batteries of tests.

Animals↗
PubMedDate not supplied

DNA damage induced by auramine O in liver, kidney, and bone marrow of rats and mice, and in a human cell line (alkaline elution assay and SCE induction).

Auramine O has been reported to be carcinogenic in rats and mice. It has been reported as positive in some mutagenicity studies and negative in others. We have found that commercial auramine O is positive in inducing DNA damage in vivo in liver, kidney, and bone marrow cells. DNA damage was also induced after treatment in vitro of a human cell line. Commercial auramine O was also clearly positive for sister chromatid exchange (SCE) induction in vivo in bone marrow cells. Purified auramine was negative in terms of DNA damage and SCE induction. Our commercial auramine O had Michler's ketone as a major contaminant. This compound was capable of inducing both DNA fragmentation and an increase of SCE.

Aniline Compounds↗
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Predictive ability of the autoradiographic repair assay in rat liver cells compared with the Ames test.

Data from the literature for 25 compounds belonging to different chemical classes were collected and their potency in the autoradiographic repair assay in rat liver cells was compared with their carcinogenic potency. A very modest correlation was found between the two parameters (r = 0.36). For 21 of the compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. Even in this case the correlation was low (r = 0.40). The results are compared with those of previous studies of different short-term tests used to predict carcinogenic potency.

Animals↗
PubMedDate not supplied

Quantitative predictivity of the transformation in vitro assay compared with the Ames test.

For 59 chemical compounds, we have found homogeneous data on transformation in vitro, mutagenicity in the Ames test, and carcinogenicity. We have compared the potency in inducing transformation in vitro in hamster fibroblast cells with the carcinogenic potency and found a modest correlation coefficient between the two parameters (r = 0.37). For these same 59 compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. The correlation level was very similar (r = 0.34). The predictivity of transformation in vitro increased significantly when only compounds for which some kind of dose-response relationship was available were utilized (r = 0.65). This result stresses the importance of the quantitative aspect of the response in predictivity studies. The present study is compared with previous studies on the quantitative predictivity of different short-term tests. Our work is not definitive, but gives an idea of the possible type of approach to the problem of comparing quantitative predictivities.

Animals↗
PubMedDate not supplied

[An effective immunodepressive treatment for demonstrating in allogeneic mice the tumorigenic properties of cells grown in vitro (author's transl)].

Short intensive treatment with N-diazoacetylglycine amide (DGA) before the inoculum, followed by prolonged daily administration of L-asparaginase (Asnase), was tested for its ability to elicit tumorigenic properties of fibroblast-like cells cultured in vitro. With this treatment progressive tumor growth was obtained in allogeneic mice injected with cells of a transformed subline. Results show that combined use of DGA and Asnase affords a higher probability of proving in vivo the tumorigenic properties of injected cells than in newborm or X-irradiated recipients. Experimental data indicate that L-asparagine depletion does not inhibit the in vitro growth of fibroblast-like cells.

Animals↗
PubMedDate not supplied

Direct interaction with cellular targets as the mechanism for chromium carcinogenesis.

The carcinogenic activity of chromium appears to be due to its direct interaction with cellular targets and not to nonspecific solid-state carcinogenesis. Chromium was evaluated at 2 valences, Cr+3 (as CrC13) and Cr+6 (as K2Cr2O7), for its toxicity, transforming activity, and ability to induce chromosomal aberrations in tertiary cultures of mouse fetal cells. The ID50 (dose for 50 percent inhibition of cell growth) of Cr+3 was approximately 4 times greater than that of Cr+6 after 96 h of exposure, and about 29 times greater than that of Cr+6 after 1 h of exposure. At equitoxic concentrations, both chromium valences induced the same degree of morphologic changes and alterations of growth behavior, but Cr+6 produced more chromosomal aberrations. Using autoradiography in an established cloned line of mouse cells, unscheduled DNA synthesis was observed in cells previously exposed to Cr+6 but not in cells previously exposed to Cr+3.

Animals↗
PubMedDate not supplied

Alkaline DNA fragmentation in vivo: borderline or negative results obtained respectively with 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene.

Using the in vivo DNA damage alkaline elution assay, a satisfactory correlation with carcinogenicity in the same target organ has been previously shown for a variety of chemical agents. This work was intended to enlarge the exploration of the predictivity of this test. Benzo[a]pyrene (BP) was found negative for damage to liver DNA of mice and rats, and 7,12-dimethylbenz[a]anthracene (DMBA) negative for damage to liver and bone marrow DNA of mice and slightly positive for damage to mammary gland DNA of young female rats. The results were found to be correlated with the extension of DNA arlyation in target organs in similar experimental conditions. From carcinogenicity data reported in the Survey of Compounds Which Have Been Tested for Carcinogenic Activity (vols. 1961-1973) BP and DMBA were both found to be essentially negative as liver carcinogens; however, DMBA was a potent carcinogen in inducing mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

A general overview of the process of carcinogenesis.

A general synthetic overview of the process of carcinogenesis is presented. The following points are discussed: the uniqueness of tumor disease with respect to other pathologies; tumors viewed as a pathology of the transduction system of signals that regulate the communal life of the cells of multicell organisms; the tumor as a genetic disease of somatic cells; carcinogenesis as a multistage event; the fundamental role of physiologic and pathologic rhythms of cell proliferation in the modulation of tumor incidence; mechanisms entailed in the maintenance of genome integrity; mechanisms involved in the protection of genome integrity from exogenous and endogenous causes of degradation of the genetic message.

DNA Repair↗
PubMedDate not supplied

Cancer prevalence in the elderly. ITAPREVAL Working Group.

AIMS AND BACKGROUND: To describe the cancer prevalence in elderly Italian people and analyze the differences, if any, with the prevalence among younger subjects. METHODS & STUDY DESIGN: The cancer prevalence among elderly patients (65 years and over), the three age classes encompassing elderly age (65-74 years, 75-84 years, 85 years and over) and younger patients (0-64 years) was computed using the PREVAL method on the basis of the incident cases over the period 1976-1992 followed up to 31 December 1992 (prevalence reference date). Data were collected by 11 Italian cancer registries. RESULTS: The observed prevalence figures for all cancers (except skin epitheliomas), both sexes combined and considering the whole elderly group, were 1,090 and 3,601 cases per 100,000 one and five years since diagnosis, respectively; the prevalence increased up to the 75-84 age group and showed a slight decrease after age 85. With regard to specific cancer sites, in men bladder and prostate had the highest prevalence 5 years from diagnosis (more than 800 cases per 100,000), followed by colon and lung (about 500 cases per 100,000) stomach and rectum (about 300 cases per 100,000); in women breast cancer ranked first (more than 1,000 cases per 100,000), followed by colon (about 350 cases per 100,000), corpus uteri, stomach and rectum cancers (between 150 and 200 cases per 100,000). For all malignancies and the two sexes combined the prevalence figures were about six times higher in the older than in the younger age group. CONCLUSIONS: These figures confirm the important role of aging in determining the increase in cancer prevalence. The resulting prevalence figures clearly indicate the cancer burden placed on health care services; moreover, the figures will probably increase in the next decades due to a possible improvement in survival and to the dramatic aging of the population, assuming a stable trend for incidence rates. This picture will represent a major challenge for politicians and those dealing with health care planning and social policies in general, especially in the light of the reduction of the available financial resources and the specific features of medical and social needs in the elderly.

Adolescent↗
PubMedDate not supplied

Signaling protein networks as targets of new antineoplastic drugs.

In-depth analysis of molecular regulatory networks in cancer holds the promise of improved knowledge of the pathophysiology of tumor cells so that it will become possible to design a detailed molecular tumor taxonomy. This knowledge will also offer new opportunities for the identification and validation of key molecular tumor targets to be exploited for novel therapeutic approaches. Some signaling proteins have already been identified as such, e.g. c-Myc, Cyclin D1, Bcl-XL, kinases and some nuclear receptors. This has led to the successful development of a few function-modulatory drugs (Glivec, SERM, Iressa), providing proof-of-principle of the validity of this approach. Further developments are likely to derive from "-omic" approaches, aimed at the understanding of signaling networks and of the mechanism of action of newfound lead molecules. High-throughput screening of small drug-like molecules from combinatorial chemical libraries or from microbial extracts will identify novel, "intelligent" drug candidates. An additional medicinal chemistry strategy (via 40-50 unit rosary-bead chains) has the potential to be much more effective than small molecules in interfering with protein-protein interactions. This may lead to considerably higher selectivity and effectiveness compared with historical approaches in drug discovery.

Antineoplastic Agents↗
PubMedDate not supplied

CA-125 monitoring in the management of ovarian cancer.

In 100 ovarian cancer patients serum CA-125 was monitored during treatment and follow-up to verify the prognostic value of its pre-surgery marker level and the usefulness of the test for disease monitoring. A low pre-operative CA-125 was not associated with improved survival or progression-free survival. A significant survival advantage was evident for patients in whom the marker had decreased during treatment, compared to patients in whom the antigen remained unchanged or increased. In 40 patients CA-125 was measured before second look laparotomy: the marker was negative in 100% of patients in, pathological complete response and in 53.5% of patients with residual disease at second look. A marker increase was evident in 32 of 41 patients with either progressive or recurrent disease, and in 17 patients the CA-125 increase was documented from 1 to 9 months before clinical evidence of progression. The pre-operative level of CA-125 did not appear to be of prognostic value. However, the monitoring of CA-125 during treatment and follow-up can provide a reliable method of assessing response and prognosis. CA-125 monitoring is particularly useful for early detection of recurrence.

Adult↗
PubMedDate not supplied

Invasiveness and chemotactic activity of oncogene transformed NIH/3T3 cells.

The role of oncogenes in the acquisition of invasive and metastatic capabilities is controversial. Interactions with basement membranes are critical in the process of tumor invasion and metastasis. We compared the ability of 3T3 cells transformed by oncogenes involved in various stages of signal transduction to invade a reconstituted basement membrane in vitro and to grow in a three dimensional basement membrane gel (matrigel). Cell lines transformed by various oncogenes and oncoviruses: v-sis (a growth factor), v-erb-B (a truncated EGF receptor), Moloney sarcoma virus (v-mos: a protein kinase homologue), mutated c-ras oncogenes (G protein homologues), FBJ virus (v-fos: a nuclear protein) were investigated. All transformed cell lines were able to invade in the chemoinvasion assay, where a layer of matrigel is coated onto chemotaxis filters. FBJ/3T3 were the least invasive and SSV/3T3 the most invasive. Control 3T3 cells could not cross the matrigel barrier. All transformed cells grew on matrigel forming invasive, branching colonies, whereas control 3T3 were unable to grow in matrigel. Cells transfected with the v-erb-B gene grew as multilayers inside matrigel. Invasiveness and growth on matrigel were accompanied by a high chemotactic response to laminin (LN) in all transformed lines. These results suggest that invasion and growth on matrigel, together with migration to LN, are induced by a large spectrum of oncogenes. When 3T3 cells were transfected with v-sis oncogene under the transcriptional control of the metallothionein (MMT) promoter and exposed to Zn++, their in vitro invasiveness was specifically increased by around 3 fold. These findings provide further evidence supporting a direct role of the v-sis oncogene in the invasive phenotype.

Cell Transformation, Neoplastic↗
PubMedDate not supplied

Interferons inhibit chemotaxis of transformed cells and their invasion of a reconstituted basement membrane.

Tumor cell migration and invasion are critical steps in the complex process of metastasis formation. It has been demonstrated that interferons (IFNs) inhibit the motility of human fibroblasts. In the present investigation we tested the effect of human leukocyte IFN and murine fibroblast IFN on the chemotactic migration of transformed and tumor-derived cells towards fibroblast conditioned medium. We were able to show that IFNs preferentially inhibit the chemotaxis of transformed and tumor-derived cell lines when compared to control fibroblasts. Inhibition was dose-dependent and most tumor cell strains were sensitive to concentrations of IFNs 10- to 100-fold lower than fibroblast cultures. Furthermore, leukocyte interferon was able to inhibit the invasion of transformed 3T3 fibroblasts through a gel of reconstituted basement membrane (Matrigel). These effects could be related to the antineoplastic activity of interferon.

Basement Membrane↗
PubMedDate not supplied

A procedure for the assay of DNA damage in mammalian cells by alkaline elution and microfluorometric DNA determination.

The microfluorimetric assay of Kissane and Robins (J. Biol. Chem. 233, 184-188, 1958) has been modified to monitor DNA content in alkaline elution fractions. The elution profiles of DNA from treated and control cultured cells demonstrated a good correlation whether DNA in the elution fractions was determined by the fluorometric method or by measuring its radioactivity. The DNA recovery was of about 80% and the measured material was DNase digestible.

Cell Line↗
PubMedDate not supplied

Major discrepancies between results obtained with two different methods for evaluating DNA damage: alkaline elution and alkaline unwinding. Possible explanations.

The fluorometric assay of DNA alkaline unwinding, developed by Birnboim and Jevcak (Cancer Res 41: 1889-1892, 1981) was applied to rat liver DNA, after treatment in vivo. N-nitrosodimethylamine, for which DNA damage in rat liver has been extensively investigated, was tested as a standard compound. The results were in complete agreement (both in terms of damage and repair) with data from the literature and with our own results obtained with other methods of detecting DNA alkaline fragmentation. Sensitivity was also of the same order of that of usual methods, with the effect of 0.3 mg/Kg of N-nitrosodimethylamine being detectable. Other DNA damaging carcinogens such as 1,2-dimethylhydrazine, 2-naphthylamine and dacarbazine were also correctly detected. Compounds like nitrofurantoin, benzoin and caprolactam, which appeared clearly positive with the alkaline elution technique, but for which genotoxicity and carcinogenicity are doubtful (nitrofurantoin) or most likely negative (benzoin and caprolactam), gave negative results with this method. This is also in agreement with previous results, observed using a different approach to measuring DNA unwinding. On the basis of these and other observations, we suggest that, under certain conditions, the alkaline elution technique is perhaps not only sensitive to DNA breaks but also to changes in chromatin conformation. Unwinding methods could be more specific in the detection of DNA fragmentations.

Animals↗
PubMedDate not supplied

Doxorubicin cytotoxicity to P388 lymphocytic leukemia as determined by alkaline elution and established assays.

Very large variations exist in the response of individual tumors to antineoplastic agents, even when the tumors are apparently very similar from the point of view of stage and histological classification. It has been recognized for a long time that methods capable of revealing the specific chemosensitivity of individual tumors could be useful for an individual optimization of a chemotherapeutic protocol. The Tumor Colony Forming Assay (TCFA) and the Biochemical Antimetabolic Assay (BAA) have been proposed for this purpose. Their main limitation is a consequence of the fact that the capability of in vitro growth is required from cells of a tumor grown in vivo. This is often lacking or very poor in the first in vitro passages. In this work we have investigated the possibility of using a sensitive method for evaluating DNA damage, the Alkaline Elution technique (AE). Cells treated in vivo can be easily tested directly for DNA damage. No cell proliferation in vitro is required. It is not required that the measured effect is the specific cause of cell death. A P388 Doxorubicin sensitive line and a resistant subline were tested. Correct correlations between DNA damage and chemosensitivity were obtained working both in vivo and in vitro. This test could be useful for assessing the chemosensitivity in vivo of alkylating and intercalating agents.

Animals↗