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S De Flora

Publications and source records attributed to S De Flora.

At least 145 records · Page 8Linked to original sources
PubMed1982

Selective deactivation of ICR mutagens as related to their distinctive pulmonary carcinogenicity.

The mutagenicity patterns and the metabolic behaviour of 4 structurally related ICR compounds were investigated using the Salmonella/microsome test. ICR 191 and ICR 170 reverted 4 his- strains (TA1537 greater than TA100 greater than TA98 and TA1538), while ICR 191-OH and ICR 170-OH reverted TA1537 only, with a narrow range of mutagenic activity. Although all the products tested were shown to contain a common mutagenic impurity, analysis of chemicals fractionated by h.p.l.c. provided evidence that pure ICR 191-OH and ICR 170-OH also induce frameshift errors. The mutagenic activity of all the 4 ICR compounds, as well as of their common impurity, was decreased in the presence of S-9 mix containing rat liver S-9 fractions, a trend confirmed by h.p.l.c. of ICR/S-9 mixtures. Despite the greater mutagenic potency in the absence of metabolic systems, ICR 191 was deactivated far more efficiently and rapidly than ICR 170 by a variety of mouse (liver greater than lung) and rat (liver greater than testis greater than kidney greater than lung greater than striated muscle greater than spleen) S-9 fractions. Mouse preparations were more effective than the corresponding rat preparations. Aroclor 1254 strongly stimulated tha activity of th NADPH-requiring enzymes responsible for ICR deactivation. H.p.l.c. analyses ruled out interconversion among the 4 ICR compounds in the presence of liver S-9 fractions, while revealing the appearance of new distinct peaks for ICR 191, ICR 170 and ICR 170-OH. The selective metabolic deactivation of ICR compounds may be related to the findings of previous carcinogenicity studies (1-3) which showed the induction of lung adenomas following i.v. but not i.p. administration of ICR 170. Conversely, ICR 191 and ICR 191-OH showed no activity even when administered i.v. Since intercalation of ICR compounds into DNA is the molecular basis for both mutagenic and antitumor activities (4), their distinctive metabolic reactivity may be also responsible for the differential efficacy in pharmacological assays.

Aminacrine↗
PubMed1981

Interplay of cell and serum immunologic markers in chronic persistent or active hepatitis B.

Immunologic markers associated with hepatitis B virus (HBV) infection (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-delta) were tested by radioimmunoassay of serum from chronic hepatitis patients. The corresponding liver biopsy samples were examined for the presence of HBsAg, HBcAg, and delta antigen in the cells by direct immunofluorescence and by electron microscopy. Seventy patients were selected for the presence of both circulating HBsAg and anti-HBc. Comparison of chronic persistent (CPH) and chronic active (CAH) hepatitis showed a significantly greater frequency of intracytoplasmic HBsAg in CPH, especially in the absence of intranuclear HBsAg, and a greater frequency of intranuclear delta antigen and/or circulating anti-delta in CAH. The delta/anti-delta system was almost systematically associated with serum anti-HBe. At variance with HBeAg/anti-HBe, delta/anti-delta found significantly more frequently in patients originating from Southern rather than from Northern or Central Italy. The prevalence of both these immunologic systems was related to the age of the patients.

Adolescent↗
PubMed1981

Variation of the frameshift activity of a mutagen (ICR-191) following nitrosation in human gastric juice.

The acridine half-mustard mutagen ICR-191 elicits peculiar frameshift mutations in S. typhimurium, which are greatly decreased in the presence of rat liver preparations. Following in vitro preincubation of ICR-191 with sodium nitrite and human gastric juice, these patterns of mutation are replaced by frameshift errors requiring metabolic activation and showing a different molecular specificity.

Aminacrine↗
PubMed1981

Relationships between mutagenic potency, reversion mechanism and metabolic behaviour within a class of chemicals (hydrazine derivatives).

Homogeneous mutagenicity data, available for 16 hydrazine derivatives assayed in the Salmonella/microsome test, were tentatively associated with their chemical structure. Some possible relationships were detected between chemical features and the following parameters in vitro: (a) mutagenic potency, expressed as revertants per micromole compound, which varied over a 3200-fold range without S-9 mix and a 7000-fold range with S-9 mix; (b) reversion mechanism, as inferred from the selective sensitivity of 5 Salmonella typhimurium tester strains; (c) metabolic behaviour in the presence of S-9 mix containing rat liver, mouse liver or mouse lung /-9 fractions from animals treated with Aroclor-1254.

Animals↗
PubMed1981

Study of 106 organic and inorganic compounds in the Salmonella/microsome test.

One hundred and six compounds, subdivided into 12 chemical classes (5 polycyclic aromatic hydrocarbons, 7 epoxides and N-oxides, 5 nitro aromatics and heterocycles, 12 aromatic and heterocyclic amines, 2 azo compounds, 17 hydrazine derivatives, 16 miscellaneous aliphatics, 5 miscellaneous heterocycles, 11 miscellaneous organics, 11 hexavalent and 7 trivalent chromium compounds, 8 miscellaneous inorganics), were studied in the Salmonella/microsome test. Fifty-eight of them (54.7%) were found to be mutagenic and 4 additional compounds (3.8%) yielded a positive response following nitrosation in human gastric juice. The results are presented in a tabulated form, providing the following information for each test compound: (a) mutagenic response in 5 S. typhimurium his- strains (TA1535, TA1537, TA1538, TA98, TA100); (b) range of activity for positive compounds or maximum dose tested for negative compounds (in nmol/plate); (c) mutagenic potency (in revertants/nmol compound), varying over a 6.5 x 10(6)-fold range; (d) effect of S-9 mix containing rat (Aroclor)liver S-9 fractions on the mutagenic response (activation, increase, no change or decrease); (e) remarks concerning the influence of other metabolic systems (up to 10 different rat tissue S-9 fractions, mouse S-9 fractions, human S-9 fractions, cell preparations or biological fluids), the interaction between different compounds, the stability and the formation of mutagenic derivatives in human gastric juice and other experimental details. Overlapping of mutagenicity and carcinogenicity data was not evaluated, since the experimental protocol intentionally included a number of non-carcinogenic mutagens and of non-mutagenic carcinogens, with the aim of explaining in some cases the conflicting nature of in vivo and in vitro conclusions.

Animals↗
PubMed1981

DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity.

Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydrazine, phenelzine, hydralazine, dihydralazine, carbamylhydrazine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydrazine) were tested for DNA-damaging activity by the alkaline elution technique and for mutagenic activity in the Salmonella-microsome (Ames) test. The first nine compounds listed (56%) were found to induce a significant DNA fragmentation in the liver and/or in the lung of i.p.-treated male Swiss mice. The DNA-damaging potency varied over an approximately 30-fold range. Thirteen of the first 14 compounds listed (81% of the total), isocarboxazid being inactive, were positive in the Ames test, with a broad range of activity towards the five bacterial strains of Salmonella typhimurium used (TA1535, TA100, TA1537. TA1538, and TA98) and of metabolic behavior in the presence of S-9 mix containing rat liver, mouse liver, or mouse lung postmitochondrial preparations from Aroclor-treated animals. The mutagenic potency varied over an almost 7000-fold range. For 11 of the 16 hydrazine derivatives tested, homogeneous carcinogenicity data (induction of pulmonary tumors in mice chronically treated p.o.) were available from literature. Elaboration of these data showed that carcinogenic potency varied over an approximately 1900-fold range. The five most potent carcinogens were all positive in the DNA damage test. Their carcinogenic potency varied over a 130-fold rage and their DNA-damaging potency varied over a 22-fold range. DNA-damaging potency seemed to vary on a more compressed scale, but regression analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, while a lack of correlation was found between mutagenic and carcinogenic potencies. There was no correlation between DNA-damaging and mutagenic potencies.

Animals↗
PubMed1980

Effect of human gastric juice on the mutagenicity of chemicals.

10 mutagens were assayed in the Salmonella test after a pre-incubation step with human gastric juice. Such treatment affected the activity of 4 compounds, with different mechanisms, either in the sense of deactivation (sodium azide and sodium dichromate), of stabilization (captan), or even of potentiation (ICR-170). Conversely, the mutagenicity of other compounds (folpet, sodium nitrite, ICR-191, nitrofurantoin and a related drug) was unchanged. The stability of 2 carcinogens requiring metabolic activation, namely benzo[a]pyrene and aflatoxin B1, provided evidence that pre-incubation of compounds with gastric juice is compatible with the subsequent addition of liver post-mitochondrial preparations, thus reproducing in vitro 2 consecutive metabolic steps occurring in the organism. These findings lead us to report an improved correlation between assays in vivo and in vitro, in particular by explaining the lack of carcinogenicity of some mutagens introduced orally or by gastric intubation. Therefore, the Salmonella/gastric juice test is proposed as an additional assay for predicting the potential health hazards of chemicals.

Biotransformation↗
PubMed1980

Formation of mutagenic derivatives from nitrite and two primary amines.

Sodium nitrite and two primary aromatic amines, viz. amino antipyrine (AAP) and aniline, were preincubated in vitro with human gastric juice. The resulting derivatives -- presumably diazonium salts -- were directly mutagenic in the Salmonella test. The mutagenic response was more pronounced in the case of AAP, while toxic effects narrowed the range of activity of the aniline derivative. These patterns are consistent with the findings of independent colorimetric analyses, showing that the AAP derivative is more stable at 37 degrees C than the aniline derivative.

Ampyrone↗
PubMed1980

Mutagenicity of cimetidine in nitrite-enriched human gastric juice.

A mutagenic response was obtained in the Salmonella/microsome reversion test by preincubating sodium nitrite and cimetidine in human gastric juice from untreated individuals, or even by adding nitrite to gastric juice samples from patients receiving cimetidine. Both base-pair substitutions (strains TA1535 and TA100) and, though very weakly, also frameshift errors (TA1537, TA1538 and TA98) were induced by such reaction. Mutagenicity was not affected by S-9 mix containing rat liver homogenates, neither in the sense of activation nor of deactivation. The optimal reaction occurred at high equimolar concentrations of the two precursor compounds, under physiological pH and temperature conditions and within a short time of contact. Ascorbic acid was efficient in preventing the formation of mutagenic nitrosoderivative(s).

Anti-Ulcer Agents↗
PubMed1980

Mutagenicity and toxicity of chromyl chloride and its vapours.

Chromyl chloride (CC), a liquid Cr6+ compound suspected of carcinogenic activity, was assayed for mutagenicity in the Ames reversion test. Due to its high volatility and toxic and corrosive properties, handling of CC required particular precautions. The liquid phase of CC elicited dose-related mutations in Salmonella typhimurium, strain TA100, although it had a limited range of activity because of its toxicity to the bacteria. The mutagenic potency and the toxic activity were of the same order of magnitude as all the water-soluble Cr6+ compounds so far tested. Toxic and mutagenic activities could also be clearly detected by using a variety of modifications of the Ames test in CC vapours which indicates the particular danger of this chromium compound. In analogy with the other Cr6+ compounds previously tested in this laboratory, all the effects observed were decreased in the presence of S-9 mix containing rat liver post-mitochondrial fractions.

Chlorides↗
PubMed1979

Epidemiological survey of hepatitis B virus infections in various groups of population.

An epidemiological survey of hepatitis B virus (HBV) infection has been carried out from 1974 up to 1978 in four laboratories, with the aim of identifying high-risk groups in the population. Radioimmunoassay procedures were used in order to detect the hepatitis B surface antigen (HBsAg) and the corresponding antibody (anti-HBs) in serum samples from over 100,000 individuals of various geographical origin (mainly from Ligury or from other areas in Northern Italy). The groups of population under monitoring included: individuals without hepatic illness just after admittance into hospitals (these groups were found to be adequately representative of the corresponding open population), groups of children and boys from the open school population, individuals living in various communities (foundling hospital, children college, recruits, institutionalized old people, subnormal individuals and their assistance staff), non-assistance working categories (workers from metallurgical and chemical industries, shipped seamen), hospital assistance personnel, dialyzed and transplanted renal patients, blood donors. The results obtained showed a considerable variability of HBV infections among the examined groups of population. In particular, the frequency of HBsAg and/or anti-HBs detection appeared to be significantly affected by each of the following epidemiological parameters: geographical area, sex, age, pregnancy, life in communities and contacts with hepatitis patients, mental deficiency, non-assistance working activities, assistance activity in the hospital environment, hemodialysis and transplants, selection of population groups by HBsAg screening.

Adolescent↗