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C F Cesarone

Publications and source records attributed to C F Cesarone.

At least 37 records · Page 2Linked to original sources
PubMed1988

Depletion of adenosine diphosphate-ribosyl transferase activity in rat liver during exposure to N-2-acetylaminofluorene: effect of thiols.

The exposure of rats to a feeding regimen containing N-2-acetylaminofluorene (2AAF) causes an accumulation of lesions on liver DNA and a progressive impairment in DNA repair capacity. We used the in vivo experimental model of Teebor and Becker (Cancer Res., 31:1-3, 1971) with the carcinogen given to rats during four consecutive cycles, each one composed of 3 weeks of treatment and 1 week of recovery. The extent of DNA damage and repair was determined during each cycle by the alkaline elution technique. The results obtained showed that the number of alkalilabile sites in DNA is significantly enhanced after the first cycle and remains increased during following cycles. Since ADP-ribosyl transferase (ADPRT) is known to play a central role in the response to DNA damage, we investigated the effect of 2AAF on this enzyme during the carcinogenic process. The activity and the structure of ADPRT were analyzed using the activity gel and Western blot techniques. The catalytic band with a molecular weight of 116,000, clearly evident in liver extracts of control rats, was no longer detectable after one cycle of exposure to 2AAF returning progressively to an almost normal level within the last two cycles. When the aminothiol N-acetyl-L-cysteine (NAC) was added to the 2AAF diet, the extent of DNA damage was drastically reduced, and DNA repair activity preserved for a longer period. In addition, the loss of ADPRT was not observed after the first cycle, but delayed to the end of the second, indicating that NAC exerts a protective effect on DNA and on ADPRT. Such effect was not evident when NAC was substituted by glutathione. The analysis of liver extracts on Western blot showed that the ADPRT immunoreactive band was almost undetectable after the first cycle suggesting that the loss in enzyme activity could be due to a block in de novo synthesis of the enzyme and not to an inhibition of its activity.

2-Acetylaminofluorene↗
PubMed1987

Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection.

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.e., a tryptophan pyrolysate product, aflatoxin B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxification mechanisms are more efficient in rats and mice.

Animals↗
PubMed1986

Effect of glutathione and N-acetylcysteine on hepatocellular modifications induced by 2-acetylaminofluorene.

The exposure of rats to a dietary regimen containing 2-acetylaminofluorene induces a sequence of hepatocellular alterations leading to the development of preneoplastic nodules. Groups of 2-acetylaminofluorene-treated rats were given glutathione or N-acetylcysteine to evaluate the effects of these different thiols on the sequence of events that originate transformed cells. It is well known that intracellular thiols protect biological macromolecules from scavenging free radicals and electrophilic compounds produced by the metabolism of chemical agents. Male Wistar rats were maintained on a feeding regimen containing 0.05% 2-acetylaminofluorene. The diet of 2 groups of 2-acetylaminofluorene-treated animals was supplemented with either 0.1% glutathione or N-acetylcysteine. The effects in the liver of the exogenously supplied thiols during 2-acetylaminofluorene treatment were assessed evaluating DNA damage, glutathione levels, activity of marker enzymes glucose-6-phosphatase, gamma-glutamyltranspeptidase, and glutathione-S-transferase, survival rates, and development of salivary gland tumors. Our results demonstrate that the mortality due to 2-acetylaminofluorene exposure was reduced or completely abolished by thiols and that the development of salivary gland tumors was inhibited. Exogenously supplied thiols significantly reduced DNA damage as assessed by alkaline elution. At the doses employed, glutathione and N-acetylcysteine induce early stimulation of glutathione-S-transferase, had little effect on the loss of glucose-6-phosphatase activity and scanty influence on the net increase in gamma-glutamyltranspeptidase activity.

2-Acetylaminofluorene↗
PubMed1984

Collagenase perfusion of rat liver induces DNA damage and DNA repair in hepatocytes.

Evidence is presented that the collagenase perfusion of adult rat liver results in significant damage to nuclear DNA as evaluated by the alkaline elution technique. The extent of the damage is related to the perfusion time as well as to the clostridial enzyme preparation used. The DNA structure of isolated cells is almost completely repaired within 12 h of their culture in chemically defined medium.

Animals↗
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↗