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M Pala

Publications and source records attributed to M Pala.

46 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

[GIST: surgical treatment of 34 cases].

In our Department of General Surgery 34 patients underwent surgery for GIST from 1983 to 2002. In stomach (21 cases) we performed: 7 local resections, 7 partial gastric resections, 5 total gastrectomies, 1 total gastrectomy + splenopancreatectomy, 1 diagnostic laparoscopy with biopsy. In small bowel (5 cases) we performed a typical intestinal resection, while in colon localization (4 cases) 2 anterior colorectal resections and 2 right partial colectomies. In duodenal and omental localization (2 cases each) we performed local resection. There was no operative mortality or morbidity. Actual survival is 67.6%. Prognostic prediction on the basis of histological findings is difficult, thus after surgery we suggest a long last follow-up.

Actuarial Analysis↗

Evidence for a fast repair of apurinic sites induced by N-nitroso-dimethylamine in rat liver DNA.

Sprague Dawley male rats were treated with N-nitroso-dimethylamine and the damage induced in liver DNA was investigated using the in vivo DNA alkaline elution assay. Determination of the number of single stranded breaks after different incubation periods in alkali showed that most of them (approximately equal to 95%) were alkali-labile sites, with a half-life of about 33 min, as expected for apurinic sites. The extent of DNA methylation was calculated, by assuming depurination of N-7-methylguanine to be the rate-limiting step for breakdown of DNA. The amount of DNA fragmentation observed accounted for only one fifth of N-7-methylguanine. The calculation could be made to correspond to the extent of methylation determined experimentally, by assuming the occurrence of a fast repair in vivo of apurinic sites (t1/2 approximately equal to 18 min). Our hypothesis of a fast repair of apurinic sites is in agreement with the analysis of data of Peterson et al. (1974). Moreover, the rate of repair required by the level of spontaneous depurination of normal guanine at neutral pH and 37 degree C, agrees satisfactorily with our estimations.

Animals↗

[Pulmonary thromboembolism. A clinical case with unusual presentation].

The authors describe a rare case of pulmonary thromboembolism with unusual clinical findings and emphasized the large difficulty encountered in formuling a correct diagnosis in a reasonable time. A man, 60 years old, was admitted to a Medical Division of our hospital for the appearance of chest pain and epigastric pain during effort in the last year. He smoked 20 cigarettes a day and drank wine (1 or 2 litres a day). He was affected by hypercholesterolemia and in the past reported relapsed thrombophlebitis in the left leg. Four years before admission to our hospital he underwent large and small left saphenectomy. He had no cardiac events in the past. After a non significant exercise stress test the patient was treated with nitrates and asa and was discharged from the hospital. At home the symptoms increased and after 8 months the patient was admitted again to the Cardiologic Division of the hospital. At admission he reported dyspnea and chest pain at rest, not only during effort and the ECG showed negative T waves in anterior and inferior leads. Intravenous heparine, nitrates and calcium antagonists stabilized the clinical picture. The following examinations revealed: reduction of the T wave negativity at the ECG registered during chest pain; mild enlargement of the heart at the chest roentgenogram; normal value of the left ventricle and apical and midseptal by ipokinesia at the transthoracic echocardiogram; normal coronary artery at the coronary arteriography. "Vasospastic angina" was diagnosed and the patient was discharged after 20 days, asymptomatic. After 15 days he returned to the hospital again for chest pain, dyspnea, hypotension and syncope despite therapy. At physical examination he showed a painful left tibio-tarsal tumefaction, an increased and splitting second heart sound in the pulmonary area and a systolic murmur in the third and fourth left interspace. The ECG showed a severe anterior ischemia, while a new transthoracic echocardiogram revealed a considerable dilatation of the right atrium, right ventricle and the main pulmonary artery with severe tricuspid regurgitation and pulmonary hypertension (mean PAP about 50 mmHg). The following pulmonary perfusion scintigraphy confirmed the diagnosis of pulmonary embolism and the selective right and left pulmonary arteriography exhibited multiple thrombi and large intravascular filling defects. The right heart catheterization confirmed a chronic precapillary pulmonary hypertension (mean PAP = 55 mmHg). About 24 hours after these examinations the patient died because of a cardiac arrest with electromechanical dissociation. Pulmonary thromboembolism is a potentially fatal disease characterized by a largely variable clinical presentation. Frequently pulmonary embolism diagnosis is difficult especially when clinical findings are unusual. In the case observed the "typical" chest and epigastric pains associated with the electrocardiographic findings directed diagnosis towards myocardial ischemia. Also after the coronary arteriography that showed normal coronary artery, the erroneous diagnosis persisted. Pulmonary embolism was correctly diagnosed too late to begin an effective therapy. These unusual clinical findings and diagnostic mistakes are stressed and critically reviewed in the article.

Angina, Unstable↗