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M Taningher

Publications and source records attributed to M Taningher.

At least 55 records · Page 3Linked to original sources
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↗
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↗
PubMed1982

Decreased viscosity of rat-liver DNA treated by 3'-methyl-4-dimethylaminoazobenzene, detected with a new viscometric approach.

DNA damage induced in vivo by 3'-methyl-4-dimethylaminoazobenzene (3'CH3DAB) was investigated with 2 differently sensitive techniques: the alkaline elution assay and the viscometric measurement of DNA damage. 3'CH3DAB appeared to be falsely negative with the alkaline elution assay, whereas with the viscometric approach, which is about 30-50 times more sensitive, it appeared positive, and the DNA damage was dose-dependent.

Animals↗
PubMed1982

Comparison between sensitivity of a viscometric method and sensitivity of the alkaline elution assay for the determination of DNA damage induced by dimethylsulfate in vitro.

DNA damage induced by dimethylsulfate (DMS) was measured with a new oscillating crucible viscometer, having a U-shaped circular channel. Rat liver nuclei were treated in vitro. Viscosity was measured by lysing nuclei in an aklaline lysing solution (pH 12.5; 25 degrees C). Nuclei were lysed immediately in the viscometer and released DNA started to uncoil. In control samples the viscosity increased very slowly with time, reaching a maximum only after about 8 h. A progressively more rapid increase in viscosity was seen with increasing concentrations of DMS. The time of DNA disentanglement was sensitive to about 30 times less breaks than the alkaline elution assay.

Animals↗
PubMed1981

DNA-damaging activity in vivo and bacterial mutagenicity of sixteen aromatic amines and azo-derivatives, as related quantitatively to their carcinogenicity.

Sixteen aromatic amines and azo-derivatives were studied. They were: benzidine; 2-acetylaminofluorene; 3'-methyl-p-dimethylaminobenzene; o-aminoazo-toluene; p-dimethylaminoazobenzene; 2,4-diamino-toluene; 4,4'-oxydianiline; 2,4-diaminoanisole; 4,4'-methylenedianiline; 2-naphthylamine; Auramine O; Rhodamine B; Ponceau MX; 1-naphthylamine; p-aminoazobenzene and aniline. The compounds were examined for their capability to induce alkaline DNA fragmentation in rat liver after treatment in vivo, for their mutagenicity in the Salmonella strains TA 98 and TA 100, for their acute toxicity and for their carcinogenicity in mice and rats. For each parameter a quantitative potency index was established, and the correlation existing amongst the different parameters investigated. Only mutagenicity in the strain TA 98 was slightly correlated with carcinogenic potency (r = 0.408). DNA fragmentation and toxicity were not correlated with carcinogenicity. A significant correlation was found between DNA fragmentation and toxicity (r = 0.539). No correlation was found between DNA fragmentation and mutagenicity. The lack of correlation between DNA fragmentation and carcinogenicity is in contrast with previous results obtained with a family of hydrazine derivatives (12) and a group of nitrosocompounds (22). For these two groups of chemicals correlation between DNA fragmentation and carcinogenicity existed, but not between carcinogenicity and mutagenicity in the Ames' test. It is suggested that short term tests can perform very differently for different classes of chemicals.

Amines↗
PubMed1980

Detection by alkaline elution of rat liver DNA damage induced by simultaneous subacute administration of nitrite and aminopyrine.

DNA fragmentation induced in the livers of rats by oral treatment with NaNO2 and aminopyrine was evaluated by the alkaline elution technique. Whereas simultaneous administration of the two compounds in a single dose produced only a minimal increase of the DNA elution rate, their intake with drinking water for 20 successive days caused DNA fragmentation comparable to that observed after a single ip injection of 10-20 mg/kg N-nitrosodimethylamine. Either NaNO2 or aminopyrine alone induced borderline DNA damaging effects, if any, in both rats receiving a single dose and those treated for 20 successive days.

Aminopyrine↗
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↗
PubMed1978

A practical procedure for testing DNA damage in vivo, proposed for a pre-screening of chemical carcinogens.

The alkaline elution method was adapted to the evaluation of DNA damage induced in vivo through a practical and reliable microfluorometric procedure, without any need for tissue pre-labeling. The DNA damage induced in vivo by treatment with a single dose of N-nitrosodimethylamine (DMNA), N-methyl-N-nitroso-urea (MNU), 1,2-dimethylhydrazine (DMH) or cycasin has been detected in different organs of mice or rats. The results obtained are rather consistent with the organotropism of these carcinogens, and show a satisfactory dose dependent of DNA damage. DMH and cycasin, both negative in the Ames' Salmonella/microsome mutagenicity test, are clearly positive with in vivo DNA damage/alkaline elution assay. This latter method, complemented with other short-term tests, may play a useful role in the pre-screening of chemical carcinogens.

Animals↗
PubMed1975

Sequential stimulation of nuclear RNA polymerase activities in livers from thyroidectomized rats treated with triiodothyronine.

A single ip injection of triiodothyronine (T3; 30 mug/100 g BW) to thyroidectomized rats markedly stimulates RNA synthesis in isolated liver nuclei. The increased level of RNA synthesized in vitro by isolated nuclei does not depend on a reduced degradation of the nascent RNA molecules, since ribonuclease activities are not affected by the administration of T3. In addition, our results have confirmed previous findings of Tata et al. that the increase in nucleolar alpha-amanitin-resistant RNA polymerase I activity at low ionic strength always preceded the rise of the nucleoplasmic alpha-amanitin-sensitive RNA polymerase II activity at high ionic strength. Moreover, it has been found that a significant increase in an alpha-amanitin-resistant activity at high ionic strength occurs as early as 10 h after hormone injection. This enzyme, which forms RNA with a U to G ratio significantly higher than that of RNA synthesized by the nucleolar alpha-amanitin-resistant enzyme, is probably nucleoplasmic RNA polymerase III which is though to synthesize 5S and transfer RNAs. The possible role and the mechanism(s) of the early and concomitant increase in nucleolar and nucleoplasmic alpha-aminitin-resistant activities, and of the subsequent rise of RNA polymerase II activity following T3 administration are discussed.

Amanitins↗
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↗