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C Bolognesi

Publications and source records attributed to C Bolognesi.

At least 55 records · Page 3Linked 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

Nuclear proteins damage by alkylating agents with different degrees of carcinogenicity.

We have tried to establish a correlation between the carcinogenic potency of two alkylating compounds and specific target sites in chromatin. We have therefore compared the nuclear metabolism of radioactively-labelled methylmethanesulfonate (MMS), a relatively weak carcinogen and N-methylnitrosourea (MNU), a highly potent carcinogen in cultured primary hepatocytes which have, high microsomal drug-metabolizing activity and in V79 Chinese hamster cells which have low microsomal enzymatic activity. The modification of specific amino acid residues in acid-soluble nuclear proteins (H) and non-histone nuclear proteins (NH) was studied after exposing the cells to various doses of alkylating agents overnight. We found that at all doses, mainly the cysteine (Cys), but also to a lower extent the histidine (His) residues are methylated in both H and NH protein fractions by MMS. At high doses of MMS, traces of methylarginine and methylated lysines could be detected. MNU predominantly methylates lysine and arginine residues, the former being found mostly in H, the latter in NH. Although both hepatocytes and V79 cells metabolized radioactively-labelled carcinogen, a higher percentage of counts were incorporated by the hepatocytes; 'unusually' methylated amino acids were detectable in the hepatocyte proteins with relatively low doses of the alkylating agents but not in V79 cells. In the presence of exogenous microsomes, during exposure of V79 cells to the alkylating agents, the amount of amino acid methylation is qualitatively and quantitatively similar to that found in hepatocytes. Our data suggest a specific mechanism of protein methylation, at the level of target amino acids, for carcinogens with different potencies similar to what has been found for DNA bases. A component of the microsomal fraction (S9) may be able to enhance this effect.

Alkylating Agents↗
PubMed1985

Benzo[a]pyrene-induced DNA damage in mouse fetal tissues.

We have studied the occurrence and persistence of DNA damage in the hepatic and pulmonary tissues of fetal, newborn and adult CD1 mice exposed to selected doses of benzo[a]pyrene (BP) by utilizing the alkaline elution technique. Firstly 12-, 15- and 18-day pregnant and 1-, 7- and 82 to 85-day-old mice were treated i.p. with 10 mg/kg BP and the DNA fragmentation evaluated 4 h later. This approach indicated that, among the ages considered, 15-day-old fetuses were the most sensitive to BP genotoxicity. Therefore we concentrated on this intrauterine stage and evaluated the role of the maternal and fetal environment on the induction and the kinetics of disappearance of DNA damage by BP. BP at the dose levels of 0, 2 and 10 mg/kg was injected i.p. into pregnant females or directly into single fetuses and the fetal livers and lungs recovered 2, 4, 24 and 48 h later. According to the above protocol other 12-day-pregnant mice were treated i.p. with 500 mg/kg arochlor and their 15-day-old fetuses directly injected with the same doses of BP. The results showed that the maximum DNA damage is present at 4 h following BP treatment and it almost disappeared at 48 h irrespective of the route of BP administration. However, the decrease was not uniform and while at 48 h the lesion reached the control level in the liver, it remained slightly higher in the lung. The effects where markedly magnified in the arochlor-induced groups where the intrafetal injection of BP caused an average 2-fold increase and an earlier appearance of DNA damage in both liver and lung compared with uninduced animals. The amplified BP activity induced by arochlor was particularly evident in the lung where at 48 h there was still a significant amount of DNA damage. Since the lung is a preferential site of transplacental carcinogenic effects in CD1 mice, our results favor the conclusion that a correlation exists between DNA damage and tumor induction in the fetuses of this mouse strain.

Animals↗
PubMed1985

Methylating agents: their target amino acids in nuclear proteins.

We have tried to establish a correlation between the carcinogenic potency of four methylating compounds and their specific target sites in chromatin. We have therefore compared the nuclear metabolism of two relatively weak carcinogens radioactively labelled: dimethyl sulphate (DMS) and methyl methanesulphonate (MMS), and two potent carcinogens: N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanosine (MNNG) in cultured primary hepatocytes and the V79 Chinese hamster cell line. Cysteine (when present), and to a lesser extent histidine, were methylated by MMS and DMS not only in the total acid-soluble nuclear protein (H) but also in purified histones H1 and H3. These compounds had the same effect not only on total non-histone nuclear protein (NH) but also on purified HMG1 and HMG2 (nuclear non-histone proteins with high electrophoretic mobility). Traces of methylarginine and methylated lysine could be detected in all samples. MNU and MNNG predominantly methylated lysine and arginine residues, the former being found mostly in acid soluble, the latter in non-histone nuclear protein. Methylated cysteine and histidine were present in trace amounts. Our preliminary data suggest specific amino acid methylation at the nuclear protein level for carcinogens with different potencies, similar to what has been found for DNA bases.

Alkylating Agents↗
PubMed1983

DNA damage induced in vivo in various tissues by nitrochlorobenzene derivatives.

Mono-, di-, and trinitrochlorobenzenes were injected i.p. into albino Swiss CD1 mice. Their effects were evaluated, in brain, liver and kidney, as single-strand DNA breaks. DNA damage was recognizable 4 h after administration in vivo, and its increment seemed to be related to the number of nitro groups contained in the chlorobenzene molecule. The simple and accurate microfluorometric procedure for DNA assay associated to the alkaline elution technique improved the application in vivo, avoiding the radiolabeling of DNA.

Animals↗
PubMed1981

Evaluation of DNA damage by alkaline elution technique after in vivo treatment with aromatic amines.

The time course of DNA damage induced by in vivo administration of benzidine, 1- and 2-naphthylamine or dimethylnaphthylamine has been evaluated using an alkaline elution technique. The organs damaged by the active ultimate metabolites, produced in mice treated with aromatic amines, appear to be, in decreasing order of susceptibility, liver, kidney and lung. Single-stranded DNA breaks are still evident 12 h after a single administered dose of the compounds. A direct dose-response relationship has been obtained using increasing concentrations of aromatic amines.

Alkalies↗
PubMed1980

[Influence of the chemical structure of aromatic amines on alkaline elution of DNA].

The DNA damage induced by in vivo administration of: 2,4-dinitroaniline, ortho-toluidine and para-toluidine, was determined using alkaline filter elution of DNA. The target organs for ultimate carcinogens produced in mice appear to be the liver and the kidney. The damage was evident 4 hours after administration of a single dose of ortho- and para-toluidine. The values obtained after treatment with 2,4-dinitroaniline fall in the range of control mice.

Aniline Compounds↗
PubMed1980

[Renal and hepatic toxicity studies in mice treated with sodium saccharin: breaks in single-stranded DNA].

The renal and hepatic effects of in vivo treatment with saccharin have been determined as increased DNA elutability on filter. A direct dose-damage relationship was not observed in the kidney and in the liver DNA of treated mice. Doses of 50, 100 and 200 mg/Kg seem to induce in almost all the experiments the same level of single-stranded breaks. The DNA elutability is increased in the range 130-210 % if compared with controls.

Animals↗
PubMed1980

[Fluorometric DNA assay at nanogram levels in biological material].

A high degree of reproducibility was obtained using a simple and rapid microfluorimetric method of DNA determination. The described method evaluates the increased fluorescence after reaction of 33258 Hoechst fluorochrome with calf thymus DNA and mouse liver chromatin preparations. The routinely used preparation reagents and the subcellular components do not interfere with the reaction.

Animals↗
PubMed1980

[DNA damage and repair induced in vivo by benzidine treatment].

DNA damage was evaluated in kidney and liver of mice treated with benzidine at the dose of 150 mg/Kg. The data presented show that the liver can be considered as the target tissue more influenced by the benzidine metabolites. The maxima of DNA fragmentation in the liver and kidney were at 4 and 2 hours respectively after treatment. Moreover the induced DNA damage in kidney and liver of mice treated was evaluated in the time depending from the rate of repair synthesis.

Animals↗
PubMed1980

[Influence of structure and physico-chemical properties of chemical agents in the induction of DNA alterations: nitrochlorobenzenes].

The DNA damage induced by mono-, di-, and trinitrochlorobenzenes has been evaluated in brain of male Swiss CD1 mice. The effect seems to be related to the increased content of nitro groups substituents on the chlorobenzene molecule. This class of compounds shows a high degree of specificity for the nervous tissue if compared to well-known carcinogens as NMU and NDMA.

Animals↗
PubMed1980

[Role of aromatic amines in the induction of tumors of the urinary tract. Experimental evaluation of the DNA damage induced with naphthylamines].

DNA damage induced by 1-Naphtylamine and 2-Naphtylamine has been verified using alkaline elution technique. Single-stranded DNA breaks were evident in the liver and kidneys of mice treated within 4 hours from the injection. A difference in the organotropism of the two aromatic amines has been observed. These results improve the applicability of the technique and are interesting in order to obtain predictive evaluations on the carcinogenicity of the aromatic amines.

1-Naphthylamine↗
PubMed1979

Standardization of the alkaline elution procedure using X-ray-damaged nuclear DNA.

Structural modification of DNA were induced by X-irradiation of crude hepatic nuclei at various dose ranges to standardize DNA damage evaluated by the alkaline elution technique. This quantitative assay can be used as reference for DNA damage induced by the in vivo administration of mutagens and/or carcinogens involved in the environment.

Alkalies↗
PubMed1979

DNA damage and repair induced by diazoacetyl derivatives of amino acids with different mechanism of cytotoxicity. Correlations with mutagenicity and carcinogenicity.

Eight synthetic N-diazoacetyl amino acids, prepared by inserting a diazoacetyl group onto the alpha-nitrogen of a natural amino acid, and two natural diazoazetyl amino acids, azaserine (9-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine), have been studied by autoradiography for their capacity to induce DNA repair synthesis in mouse cells cultivated "in vitro". Dose-dependent unscheduled DNA synthesis was present in cells treated with the eight N-diazoacetyl derivatives, and was absent in cells exposed to approximately equitoxic concentrations of azaserine and DON. Azaserine and DON, unlike N-diazoacetyl derivatives, did not alkylate gamma-(4-nitrobenzyl) pyridine at an appreciable extent. When DNA damage (single stranded breaks or weak points in alkali) was measured by the sensitive technique of alkaline elution, DGA was found about 4 times as potent as azaserine and about 12 times as DON on a molar basis, but about 800 and 17,000 times as potent as azaserine and DON respectively by extrapolating to equitoxic concentrations. Carcinogenicity and mutagenicity seem to follow mainly the capability of inducing DNA damage.

Alkylation↗
PubMed1979

DNA fragmentation in some organs of rats and mice treated with cycasin.

Cycasin (methylazoxymethanol-beta-D-glucoside) is carcinogenic in several animal species. It produces a variety of malignant tumours, mainly in the liver of mice, and in the liver, kidney and large intestine in rats. It does not appear to be mutagenic in the Ames test, even in the presence of liver microsome fraction, and it is among those carcinogens (less than 10%) ranked as "false negatives" in this test. The ability of cycasin to damage in vivo liver, kidney, lung and colonic DNA of Wistar rats and C57BL/L mice was investigated by means of alkaline elution technique. Oral single-dose administration of cycasin, in the range of 50-400 mg/kg body weight, produced in the rat a clearly evident dose-dependent DNA fragmentation in the liver, and less marked damage to DNA from kidney and colon mucosa. In mice, the same treatment produced dose-dependent DNA damage only in the liver. DNA repair up to 18 h appeared to be incomplete both in mice and rats. Methylazoxymethanol acetate is considered to be an active form of cycasin. While in vivo methylazoxymethanol acetate caused DNA damage, in vitro it appeared inactive and required metabolic activation, possibly consisting in its hydrolysis by esterase activity, to be able to cause DNA fragmentation.

Animals↗