PubMed Health⌕ Search

Biomedical subjects

S Parodi

Publications and source records attributed to S Parodi.

At least 145 records · Page 8Linked to original sources
PubMed1986

Quantitative predictivity of carcinogenicity of the autoradiographic repair test (primary hepatocyte cultures) for a group of 80 chemicals belonging to different chemical classes.

In this work we have investigated the correlation existing between a short-term genotoxicity test (DNA repair in rat liver cells) and carcinogenicity in rodents. The work is in the framework of a line of thinking that considers as a possibility the utilization of the quantitative component of the information obtained from genotoxicity tests. In a preliminary report for 25 compounds belonging to different chemical classes, a correlation coefficient of 0.36 was found between carcinogenic potency in small rodents and potency in autoradiographic repair. This level of correlation is comparable with similar levels found for many other short-term tests: Ames test, alkaline DNA fragmentation in vivo, DNA adducts in vivo, morphological transformation in vitro and SCE induction in vivo. Obviously, since only 25 compounds were examined, assessment was rather uncertain, and the subdivision of the set into subsets for different chemical classes would have generated groups too small for a meaningful statistical analysis. With a much larger set (80 compounds) we hoped to be able to discriminate different predictivities for different chemical classes. This seems important because the test could be much more suitable for one given class than for another. Previous investigations with different short-term tests have shown that these differences can indeed exist and be very great. In this respect it is potentially very encouraging that the test considered here showed a fair correlation with carcinogenic potency for aromatic amines. Many other tests that we have examined so far have shown little or no predictivity for this important class of chemicals.

Animals↗
PubMed1985

SV40 transformed fibroblasts recognize the same 140 kD fibronectin chemotactic fragment as non-transformed cells.

SV40-virus-transformed human embryonal fibroblasts show an enhanced chemotactic response to the glycoprotein fibronectin. However, they recognize the same chemotactic active region as non-transformed fibroblasts. The result suggests that an enhancement of chemotaxis by fibroblasts which have been transformed with Simian Virus 40 is due not to the utilization of further chemotactic domains in the molecule, but to an increased sensitivity of the cells to the chemoattractant.

Cell Transformation, Viral↗
PubMed1985

Comparison of the chemotactic response to conditioned medium of BALB/c3T3 fibroblasts and their SV 40 transformants.

The chemotactic migration of transformed cells out of their tissue of origin might represent an essential component of tumor invasion and metastasis. In the Boyden chamber assay SV 40 virus-transformed BALB-c3T3 fibroblast (SV/3T3) showed an increased chemotactic response to fibroblasts-conditioned medium in comparison to non-transformed BALB/c3T3 cells. This was verified for a large range of incubation times and cell densities. Fibroblast-conditioned medium contains components of the extracellular matrix of connective tissue. Since organs rich in connective tissue are often the site of metastasis, the enhanced chemotaxis of virus-transformed cells to conditioned medium could contribute to explain the malignancy of these cells.

Animals↗
PubMed1985

Detection of DNA damage induced in vivo by a cross-linking agent with a circular channel crucible oscillating viscometer.

DNA damage induced in vivo by the cross-linking agent mitomycin C (MMC) was investigated with a new oscillating crucible viscometer. Viscosity was measured by lysing rat liver nuclei in an alkaline lysing solution (pH 12.5; 25 degrees C). In control samples the viscosity increased very slowly with time, reaching a plateau only after 10-12 h. The process was accelerated and the maximum viscosity was decreased by alkaline single-stranded breaks arising from methylation and subsequent depurination of DNA in vitro with dimethylsulphate (DMS). MMC, when given alone, had no evident effect on the time needed for reaching plateau viscosity but it induced a small increase in maximum viscosity. When MMC was given in association with DMS, the time of disentanglement remained unchanged (accelerated) but maximum viscosity was increased in a dose dependent way. We conclude that these data clearly confirm that the slow steady increase of the viscosity of control DNA with time reflects mainly the process of unwinding of the two strands. The speed of this process seems to depend only from the number of unwinding points in DNA (breaks).

Animals↗
PubMed1985

Assay of phenacetin genotoxicity using in vitro and in vivo test systems.

Phenacetin was assayed in a battery of five short-term tests. (1) In a DNA-repair test using various Escherichia coli strains, the drug was not directly genotoxic nor did it induce nonreparable DNA damage in the presence of rat liver S9 fractions, while it was weakly active following activation with hamster liver S9. (2) In the Ames reversion test (strains TA97, TA98, TA100, and TA102 of Salmonella typhimurium, phenacetin reverted only TA100, and only in the presence of hamster liver S9. Mutagenicity was related to the concentration both of the drug and of the above metabolic system. There was no activation with hamster kidney S9, uninduced chicken liver S9, or with a variety of liver S9 preparations from rats treated with enzyme inducers (Aroclor 1254, phenobarbital, or 3-methylcholanthrene) and/or glutathione depletors (diethyl maleate or buthionine sulfoximine). Hamster liver S9 compared favorably to rat and even more to chicken liver S9 fractions also in activating various promutagens [3-amino-1-methyl-SH-pyrido (4,3-b)-indole, 2-aminofluorene, aflatoxin B1, benzo[a]pyrene, and benzo[a]pyrene-trans-7,8-diol] and in decreasing the mutagenicity of direct-acting compounds (4-nitroquinoline N-oxide and sodium dichromate). (3) Phenacetin was borderline positive in a forward mutation test (6-thioguanine resistance) in V79 cells, only in the presence of hamster liver S9, and gave negative results in the presence of rat liver S9 or without any metabolic system. (4) Following in vivo treatment, the alkaline elution assay did not reveal any DNA fragmentation in bone-marrow cells of ip-treated mice or in liver cells of rats treated by gavage. Apparent DNA damage was instead observed in the kidneys of rats receiving the drug by gavage or in the liver following ip administration. However, the effect was prevented (liver) or reduced (kidney) by preliminary perfusion of the organs, which discards (liver) or makes uncertain (kidney) the hypothesis of a true in vivo DNA damage. (5) Phenacetin ip induced in mouse bone-marrow cells a poor yet statistically significant increase in sister chromatid exchanges.

Animals↗
PubMed1985

Orotic acid, a promoter of liver carcinogenesis induces DNA damage in rat liver.

Orotic acid, a precursor of pyrimidine nucleotide biosynthesis and a promoter for liver carcinogenesis, when fed at 1% level in a diet for 5 weeks resulted in liver DNA damage. The damage can be monitored as alkali-labile lesions using alkaline sucrose gradients as well as alkaline elution technique. Furthermore, the induced DNA damage persists for up to three weeks after withdrawal of the orotic acid diet. The fact that several skin-tumour promoters also induce DNA damage raises the question whether DNA damage is a component in tumour promotion.

Animals↗
PubMed1984

Chemotactic response of SV40 virus transformed fibroblasts to conditioned medium: dependence on time and cell number.

The ability of tumor cells to move chemotactically in response to specific stimuli may be one of the many factors which distinguish malignant from non-malignant cells. In this work we demonstrated that a SV 40 virus transformed human fibroblast cell line (SV40/WI26) has an enhanced chemotactic response to fibroblast-conditioned medium (FCM) as compared to control human fibroblasts, and this was true for different migration times and different initial cell numbers. A similar behaviour has been described for SV40 transformed mouse fibroblasts (SV3T3). Furthermore, another SV40 transformed human fibroblast cell line (SV40/WI38) has been reported to have an enhanced chemotactic response to FCM compared to the normal counterpart. We conclude that the increased chemotactic response to FCM could be well correlated with the phenotype induced by fibroblast transformation with SV 40.

Cell Count↗
PubMed1984

A method to select cell populations with enhanced chemotactic activity.

Virus-transformed and tumor cells often show a higher chemotactic activity in comparison to normal cells. Here we show that the blind-well chamber assay is an easy and rapid procedure to select cell populations with enhanced chemotactic activity. Collagen-type-specific antibodies have been applied to analyze the efficiency of cell sorting by the chemotaxis assay.

Cell Separation↗
PubMed1984

Effects of vitamin E on liver DNA.

Vitamin E, both in the form of dl-alpha-tocopherol and dl-alpha-tocopheryl acetate, was capable of inducing an increased alkaline elution rate of liver DNA from rats treated i.p. with the vitamin. This activity was clearly both dose- and time-dependent. A statistically significant effect was observed at dosages (1.25-5.00 mg/kg) that are in the range of biological activity of the vitamin in the rat (reabsorption-gestation bioassay). Moreover, the effect was observed at dosages that are clearly not toxic. An increased alkaline elution rate of DNA is usually interpreted as suggestive of DNA damage, however recent observations seem to indicate that functional modifications of chromatin packaging can also affect the elution rate of DNA.

Animals↗
PubMed1984

Quantitative correlation with carcinogenic potency of different short term tests.

The following short term parameters evaluating essentially genotoxic effects were considered: liver DNA alkaline fragmentation (DFI), morphological transformation in hamster embryo cells (TPI), and mutagenicity in the Ames' test (MPI). The internal consistency of the carcinogenicity data (OPI) was rather high (r approximately or equal to 0.8). The correlation with OPI of DFI and MPI was statistically significant but rather modest, about 0.4-0.5. The best correlation between OPI and TPI was 0.65. This level of correlation was observed only when some kind of dose-response relationship for transformation could be established. When comparisons were attempted for exactly the same 27 compounds for all three tests, a general decrease in predictability was observed. This could be mainly due to problems of representation of the ideal population of chemicals using small samples. The more general problem of the quantitative approach to the predictability of short term tests was also discussed.

Animals↗
PubMed1984

Quantitative predictivity of carcinogenicity for four short-term parameters, evaluated in rat liver: alkaline DNA fragmentation, autoradiographic repair, DNA adducts, preneoplastic nodules.

The possibility of the study of a quantitative correlation between short-term tests and carcinogenicity, instead of a qualitative one, is discussed. Four tests related to the target organ, rat liver, were considered: alkaline DNA fragmentation, DNA repair, DNA adducts and the formation of preneoplastic nodules. All the four tests showed a similar level of correlation with carcinogenic potency (r approximately equal to 0.4). With this level of correlation, the dispersion of the data appeared too large to offer a meaningful degree of quantitative predictivity of carcinogenicity, in reference to a single test. It appeared however, that the use of a battery of two or three independent short-term tests, with the above level of simple correlation, could generate a multiple correlation high enough to be potentially useful for some degree of quantitative predictivity of carcinogenic potency.

Amines↗
PubMed1983

Alkaline DNA fragmentation, DNA disentanglement evaluated viscosimetrically and sister chromatid exchanges, after treatment in vivo with nitrofurantoin.

Nitrofurantoin was not positive as a carcinogen in long term assays. In vitro it was positive in some short term tests and negative in others. We have examined Nitrofurantoin for its capability of inducing DNA damage in vivo. With the alkaline elution technique, Nitrofurantoin appeared clearly positive in all the tissues examined (liver, kidney, lung, spleen and bone marrow). In the liver we also observed some cross-linking effect. In bone marrow cells Nitrofurantoin was also clearly positive in terms of sister chromatid exchanges (SCEs) induction. DNA damage in vivo was also examined with a viscosimetric method, more sensitive than alkaline elution. With this method the results were essentially negative, suggesting that the two methods detect different types of damage. In view of its positivity in many organs and in two short term tests in vivo, the carcinogenic potential of Nitrofurantoin should be reconsidered.

Animals↗
PubMed1983

Detectability in vivo of stabilized intercalating agents with the alkaline elution technique. Comparison with in vivo sister chromatid exchange introduction.

The purpose of the work reported here was to investigate, with the alkaline elution technique, the capability of in vivo administered actinomycin D, daunomycin and mitomycin C to induce DNA damage, DNA interstrand cross-linking and DNA-protein cross-linking. The ability of these compounds to induce increases in sister chromatid exchange (SCE) in the bone marrow cells of mice was also investigated. Actinomycin D and daunomycin were active in inducing single strands breaks, while mitomycin C was inactive. Mitomycin C showed a clear DNA interstrand cross-linking activity, while this activity was absent in actinomycin D and daunomycin. All three compounds were positive for SCE induction, but mitomycin C was by far the most active compound. Our results seem to suggest that stabilized intercalating agents are often detectable with the alkaline elution technique, after treatment in vivo. However, they cannot be evaluated with the simple alkaline elution technique only. It is convenient to add to the basic method the modification for detecting cross-links. Finally, DNA interstrand cross-linking and sister chromatid exchanges could be correlated.

Animals↗
PubMed1983

Studies on DNA damage: discordant responses of rate of DNA disentanglement (viscosimetrically evaluated) and alkaline elution rate, obtained for several compounds. Possible explanations of the discrepancies.

Alkaline elution is a well-known method for detecting DNA damage. Recently we have developed a viscosimetric method that is even more sensitive than alkaline elution. Here we report that the two methods, although apparently both revealing alkaline DNA fragmentation, can give dramatically different results for a significant series of compounds. We suspect that alkaline elution might reveal not only DNA fragmentation but also the extent of disentanglement of chromatin structure, whereas this DNA disentanglement rate, when evaluated viscosimetrically , is more strictly correlated with the initiation of DNA unwinding.

Animals↗
PubMed1983

Lack of correlation between the capability of inducing sister-chromatid exchanges in vivo and carcinogenic potency, for 16 aromatic amines and azo derivatives.

16 aromatic amines and azo derivatives were studied. They were: benzidine; 2-acetylaminofluorene; 3'-methyl-p-dimethylaminoazobenzene; o-aminoazotoluene; p-dimethylaminoazobenzene; 2,4-diaminotoluene; 4,4'-oxydianiline; 2,4-diaminoanisole; 4,4'-methylenedianiline; 2-naphthylamine; auramine O; rhodamine B; ponceau MX; 1-naphthylamine; p-aminoazobenzene and aniline. Carcinogenic potency and potency in inducing sister-chromatid exchanges (SCEs) in vivo were compared. SCEs were absolutely not correlated with carcinogenic potency. A lack of correlation was also found with mutagenicity in the Ames test. On the contrary, a statistically significant correlation existed between DNA damage and SCEs.

Carcinogens↗
PubMed1983

Quantitative correlation between carcinogenicity and sister chromatid exchange induction in vivo for a group of 11 N-nitroso derivatives.

The quantitative correlation between induction of sister chromatid exchanges (SCEs) in vivo and carcinogenic potency was examined for 11 nitroso derivatives and was compared with the correlation of alkaline DNA fragmentation in liver DNA in vivo and with the Ames test. The correlation between DNA adducts and SCEs was also evaluated. DNA damage was slightly more predictive and the Ames test less predictive than SCE evaluation. The predictivity of these tests for this class of compounds was compared with the predictivity shown for different classes of chemical compounds.

Animals↗
PubMed1982

Quantitative correlations amongst alkaline DNA fragmentation, DNA covalent binding, mutagenicity in the Ames test and carcinogenicity, for 21 compounds.

21 compounds from different chemical classes were quantitatively compared for their carcinogenic potency according to 4 parameters: (1) potency in inducing covalent binding with DNA in vivo; (2) potency in inducing alkaline DNA fragmentation after treatment in vivo; (3) acute toxicity; (4) mutagenic potency in the Ames test. Establishing well-defined conditions for normalization of the different types of data and determination of the set that had to be submitted to statistical analysis appeared to be a difficult task, for which only compromise solutions were possible. A statistical analysis of the data suggested that all parameters considered were correlated with carcinogenic potency. However, we found that there are about 3 chances to 1 that carcinogenicity is better correlated with DNA covalent binding in vivo than it is to mutagenicity in the Ames test. With due precautions, even acute toxicity could be of predictive value. DNA adducts and DNA fragmentation, both in vivo, appeared to be 2 parameters strongly correlated between them. From a multivariate statistical analysis it appeared that: (1) a significant improvement of quantitative predictability is in principle obtainable with a battery of short-term test; and (2) the improvement is obtainable only if the short-term tests considered, while all correlated with carcinogenicity, are relatively independent amongst themselves.

DNA↗