Genotoxicity assessment of new synthesized acridine derivative--3,6-diamino-10-methyl-9,10-dihydroacridine.

A new synthesized acridine derivative, 3,6-diamino-10-methyl-9, 10-dihydroacridine (AcrH), was tested for in vitro reverse mutations with Salmonella TA strains, chromosome aberrations and sister chromatid exchanges (SCE) in human lymphocytes, and for in vivo chromosome aberrations in bone marrow of mice. Using the classic plate incorporation method, mutagenicity of AcrH in bacterial cells (TA97a, TA98, TA100 and TA102) was observed in the experiments performed with, and without, rat liver S9 metabolic activation. The reverse mutation assay showed no difference in mutagenic activity between AcrH and acriflavine (Acr(+)) in the test with TA97. The results of in vitro chromosome aberrations assay revealed potential clastogenicity. The test using macroculture of human lymphocytes induced mainly chromatid gaps. The experiments with human lymphocytes revealed SCE-inducing effect of AcrH and Acr(+). In an in vivo study, AcrH given intraperitoneally to Balb/c mice did not cause any significant increase in the percentage of cells with aberrations compared to the negative control.

Mutagenic activity of 3,6-diamino-10-methyl-9,10-dihydroacridine in Salmonella typhimurium cells.

Mutagenic evaluation of 3,6-diamino-10-methyl-9,10-dihydroacridine (AcrH), a new synthesized acridine derivative was undertaken using short-term in vitro test. The mutagenic potential of AcrH was evident from the reverse mutation induced in the presence and absence of S9-mix of Salmonella typhimurium TA97a, TA98, TA100 and TA102 cells. The levels of the mutagenic activity of AcrH in TA97a are comparable with that of acriflavine.

Genotoxicity evaluation of tetramethylbenzenes.

The three tetramethyl isomers of benzene (prenitene, 1,2,3,4-; izodurene, 1,2,3,5-; and durene, 1,2,4,5-tetramethylben- zene) were studied using in vitro mutagenicity and in vivo genotoxicity tests. Potency of mutate induction by these solvents was evaluated in Salmonella typhimurium cells with, and without S9-mix made from Aroclor 1254-induced rat liver S9. The potency of induction of micronuclei (MN) and sister chromatid exchanges (SCEs) by solvents was evaluated in bone marrow of mice. Izodurene displayed mutagenic potency in strains TA97a, TA98 and TA100 only in the absence of the S9-mix. In MN tests, all three tetramethylbenzenes demonstrated no clastogenic activity on the bone marrow cells. All the tested solvents were active as genotoxic compounds in the SCE tests, demonstrating a dose-response relationships.

A long-term follow-up of allergy to nickel among fixed prostheses wearers.

Skin allergic hypersensitivity to nickel is well known and well documented in the professional literature. Sixteen partially dentate patients with long-standing histories of recurrent hypersensitive skin reaction to nickel were entered into a clinical trial in 1979. All the patients received crowns or bridges made of an alloy containing 66% of nickel with porcelain fused to the metal framework. During the first three years, annual clinical dental and dermatological investigations were performed on all the subjects, including repeated patch tests. Follow-up examinations took place in 1988 and 1994. None of the subjects had any mucosal or systemic reaction following oral exposure to the nickel containing alloy, nor the exacerbations of skin lesions.

Genotoxicity of Farbasol and its component: 4-ethyltoluene.

A combination of assays for gene mutations in Salmonella typhimurium TA97a, TA98, TA100 and TA102 strains with and without rat liver activation, and for micronucleus and sister chromatid exchange (SCE) in bone marrow cells of Imp:Balb/c mice was used to provide data on the mutagenic and genotoxic properties of the mixture of aromatic solvents, known under the trade name of Farbasol. In addition, 4-ethyltoluene (the main ethylmethylbenzenic component of Farbasol) was also tested for muta- and genotoxicity. The results revealed that neither Farbasol nor 4-ethyltoluene induced an increased reverse mutation in bacterial cells or the formation of micronucleated polychromatic erythrocytes in bone marrow. However, those compounds were found to be active as sister chromatid exchange (SCE) agents.

Genotoxicity evaluation of trimethylbenzenes.

The three trimethyl isomers of benzene (hemimellitene, 1,2,3-TMB; pseudocumene, 1,2,4-TMB and mesitylene, 1,3,5-TMB) were investigated for different genotoxicity endpoints: in vitro, in the Ames test with Salmonella typhimurium TA97a, TA98, TA100 and TA102 strains in the presence and absence of rat liver S9 metabolic activation; in vivo, in the micronucleus and sister chromatid exchange (SCE) tests with bone marrow cells of Imp:Balb/c mice. Only the isomer of benzene with the methyl-group at position 1, 2, 3 was found to have mutagenic effect on S. typhimurium cells. Increase in bacterial reversions was observed in four conventional strains used in this study, but most clearly in TA97a. The mutagenic responses of 1,2,3-TMB with the SalmonellaL tester strains were observed in the experiments performed in the absence of enzymatic activation. None of the compounds had an influence on the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of mice. However, all the three compounds were observed to have a cytogenetic potential of increasing the SCE level in these cells. Significant responses in SCE induction, compared with the level of those changes in corresponding solvent-administered controls, were obtained at three test doses of 1,2,3-TMB (730, 1470, 2200 mg/kg) and 1,2,4-TMB (900, 1800, 2700 mg/kg) and at two doses of 1,3,5-TMB (1800, 2700 mg/kg). These data provided a limited evidence for the genotoxic activity of 1,2,3-TMB and inadequate evidence for genotoxic activity of 1,2,4-TMB and 1,3,5-TMB.

Mutagenic and genotoxic activity detected by the Ames, micronucleus and SCE tests under the influence of samples of dyes manufactured in Poland.

In this study, we evaluated the mutagenic and genotoxic potential of commercial samples of chemicals manufactured by Polish dyestuff industry for their ability to mutate Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102), and to induce formation of micronuclei (MN) and sister chromatid exchanges (SCE) in mice bone marrow cells. This study involved five dyes selected from a list of colorants, considered to be representative of those which were most extensively used in the trade. According to criteria listed by IARC (1984), the results obtained in this work and earlier tests of Basic Blue 26, 44045 and Direct Red 83, 29225 provided no evidence of genetic activity (all 3 tests were negative); for Acid Violet 49, 42640 and Disperse Blue 37, the evidence of genetic activity was inadequate (1 test was positive) and the tests for Acid Black 194 provided limited evidence of genetic activity (2 positive tests).

Comparison of the mutagenicity of chemical agents released during coke production.

Benzene- and acetone-extracted samples of airborne particulate matter collected in two coke plants were analysed for their content of genotoxic agents (coal tar pitch volatiles (CTPVs), polycyclic aromatic hydrocarbons (PAHs): benzo/a/pyrene, pyrene, dibenzo/a,h/anthracene, anthracene and fluoranthene) following the identification and quantification of the compounds as well as the evaluation of their mutagenic activity using in vitro reverse mutation assay. Results of determinations at the top section of coke batteries were compared. Mean concentrations of total dust, CTPVs and B/a/P were as follows: 2.06 mg/m3, 0.63 micrograms/m3 in plant A, and 2.77 mg/m3, 0.89 mg/m3 and 0.35 micrograms/m3 in plant B, respectively. All the extracts of particulate matter samples increased the induction of bacterial mutation in both +S9 and -S9 tests. The exposures to mutagenic airborne particulate matter were in the range of 98-683 rev./m3 (-S9): 714-2214 rev./m3 (+S9) in plant A, and 21-496 rev./m3 (-S9); 68-850 rev./m3 (+S9) in plant B. The correlation between mutagenic potential and concentrations of tested agents was insignificant. The coke oven emission seemed to be higher in plant A with side charging of coal.

Mastication with and without removable partial dentures: an intraindividual study.

The chewing of 22 subjects, with a total of 27 removable partial dentures (RPD) that had been used for more than 6 months, was analyzed by four different methods. The study design was an intraindividual comparison of chewing, with and without the RPDs. Chewing tests were a color mixture of two-colored gums, chewing gum bolus shaping, comminution of Optosil silicone tablets, and number of chewing strokes to first swallow of an almond. The participants were also asked some standardized questions about their eating, biting, and chewing capacity. There was no significant difference in efficiency as measured by chewing gum color mixing, chewing gum shape, and pulverization of Optosil between chewing with and without the RPDs. Significantly more strokes were needed to swallow an almond without than with the RPD in place. With their RPDs in place, all subjects could chew a sandwich and an apple, and all but one could chew whole meat. The study shows that the chewing process should preferably not be analyzed by one method only.

Non-mutagenicity of thiadiazole-1,3,4 derivatives in Salmonella typhimurium strains.

The Ames mutagenicity assay with Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102) was used to investigate the ability of five dyes (thiadiazole-1,3,4 derivatives) to induce point mutations. The results did not reveal any mutagenic effects of the tested dyes on the S. typhimurium strains. No mutagenic activity was observed in the experimental series with and without exogenous activation.

Cyanuric chloride has no genotoxic and mutagenic properties in bacteria and bone marrow cells.

Three short-term tests were used; Salmonella/microsome assay, in vivo sister chromatid exchange assay (SCE) and micronucleus assay to evaluate mutagenic and genotoxic properties of 2,4,6-trichlorotriazine; cyanuric chloride. Mutagenicity assays were carried out using the standard top agar overplay plate assay described by Maron and Ames (9). Tester strains TA97a, TA98, TA100 and TA102 were used. Compound was dissolved in 0.1 ml of DMSO and doses of 1, 10, 100 and 500 micrograms/plate were tested in the absence and in the presence of the S9-mix. From the results obtained it appeared that incubation of the test substance with the bacteria did not increase the number of His+ revertants with any of the strains of S. typhimurium, either in the absence or in the presence of the S9-mix. At the high dose level used i.e. 100 and 500 micrograms/plate, the test substance appeared to be slightly toxic for strain TA 97a (in the absence of the S9-mix), as was seen from a diminished number of revertant colonies. The SCE test was performed according to the GENE-TOX programme. No significant increase was noted in the incidence of SCE in the groups treated with all tested doses of cyanuric chloride. Thus, in this test cyanuric chloride did not induce chromosomal damage resulting in SCE formation in bone marrow cells of mice. The micronucleus assay in vivo was performed on mice bone marrow cells. The incidence of micronucleated polychromatic erythrocytes after administration of all doses of cyanuric chloride used were not statistically different (p > 0.05) as compared to negative controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential carcinogenicity assessment of alpha-aescin and phenbendasol.

Potential carcinogenic activity of alpha-aescin and phenbendasole made by "Polfa" (Poland) as well as phenbendasole produced by "Hoechst" (Germany) was studied using Salmonella/microsome test, DNA repair test and micronucleus assay. None of tested preparations were mutagenic or genotoxic what suggest that none of them possess potential carcinogenic activity. Besides, it was established that alpha-aescin exhibits strong and phenbendasol weak acute systemic toxicity for mice. Alpha-aescin and phenbendasole produced in Poland have been found to be toxic for bone marrow cells of mice but only when administered at a high dose of 80% LD50.

Immunological status of patients with denture stomatitis and yeast infection after treatment of maxillofacial tumors.

Therapeutic modalities employed in the treatment of maxillofacial malignancy, tumor resection, radiation and chemotherapy, can result in local and systemic changes in healthy oral tissues many years after anticancer therapy has been stopped. The immunologic status of a select group of nine individuals who underwent surgery of the maxillofacial region and after head and neck irradiation, with severe and persistent denture stomatitis was studied. A significant impairment of granulocyte and lymphocyte functions and increased concentrations of serum IgG, as compared to healthy controls, were found in the patients of the study group. It is concluded, that this group of patients show immunological abnormalities many years post therapy, which must be recognized by the clinician in order to effect a cure.

Genotoxicity assessment of Rokanol B2 and Rokamid R1.

Two surface-active compounds, Rokanol B2 and Rokamid R1, were examined with three types of screening tests: 1. standard Ames test in vitro using S. typhimurium TA97a, TA98, TA100 and TA102 strains; 2. micronucleus test in vivo; 3. sister chromatid exchange (SCE) on bone marrow cells of Balb C mice. Negative results of the testing, in terms of the effects of activity of both the technical preparations on S. typhimurium cells and bone marrow of Balb C mice, were found for both tested chemicals.

[Identification of potential carcinogenic dyes and intermediates on the basis of their genotoxicity]. / Identyfikacja potencjalnie rakotwórczych barwników i pólproduktów na podstawie oceny ich genotoksycznosci.

41 dyes, pigments and surface-active compounds were tested for mutagenic and genotoxic properties. It was found that 43% of the studied dyes of Polish make which belonged to the azo, triarylmethane and anthraquinone compounds were mutagenic or genotoxic. All the studied pigments and surface active compounds did not reveal potential carcinogenic activity except for NNO Dyspergator whose possible genotoxic activity needs confirmation in further study.

Genotoxicity assessment of sulfosuccinate IO-5, Rokamid MRZ 17, Rokacet RZG7P2 and Roksol TL-7 using bacteria and bone marrow rodent cells.

Three short-term tests were used for evaluation of the genotoxic activity of four surface active agents. These were: Ames, Salmonella reversion assay using 4 tester strains (TA97a, TA98, TA100 and TA102), the micronucleus test int the bone marrow of Balb C mice and in vivo sister chromatid exchange (SCE) analysis in SFIS or Balb C mice. The frequency of micronucleated PCEs did not exceed the control values in mice of both sexes after intraperitoneal administration of all four compounds. Three preparations--Sulfosuccinate IO-5, Rokamid MRZ 17 and Rokacet RZG7P2 produced a negative response in Salmonella strains gene mutation assay and SCE induction test in mouse bone marrow cells. The Roksol TL-7 induced frameshift and base-pair substitution mutations in Salmonella tester strains both with and without S9 (prepared from the liver of rats which had been pretreated with Aroclor 1254). Evidently positive results (more than a twofold increase in the number of revertants per plate) were observed in tester strain S. typhimurium TA97a (with and without S9 metabolic activation) and S. typhimurium TA100 (with S9 metabolic activation) at a dose of 0.2 microliter Roksol TL-7 per plate. Roksol TL-7 caused slight increase in the SCE level in mouse bone marrow cells. A significant increase in SCE frequency was observed at doses of 50, 75 and 100 mg/kg.

Correlation between polycyclic aromatic hydrocarbons concentration and airborne particle mutagenicity in the rubber factory.

The study was undertaken to evaluate the correlation between benzo[a]pyrene and coal tar pitch volatiles concentrations and mutagenic activity of airborne particles sampled at different workplaces of the factory producing various types of tires. The solid phase of aerosols was collected on Whatman glass-fibers filters using Staplex pumps. Coal tar pitch volatiles (CTPVs) were extracted from sample filters using ultrasonic-benzene extraction and determined by the gravimetric method. Benzo[a]pyrene (BaP) analysis was performed using high performance liquid chromatography with a spectrofluorimetric detector. The mutagenic substances were extracted from collected material with acetone. The mutagenic properties were estimated with the Ames' test using S. typhimurium strain TA98 without and with S9 fraction. At nearly all workplaces the concentrations of BaP and CTPVs were within the range of 4-61 ng/m3 and 0.11-1.26 mg/m3, respectively. Only at weighing were they much higher and amounted to 172-2261 ng/m3 for BaP and 3.05-4.07 mg/m3 for CTPVs. The highest exposure to mutagenic airborne particulate matter was found at weighing (1500 rev/m3), the mixers loading level (> 500 rev/m3) and the carbon black station (> 150 rev/m3). The air mutagenic activity at other workplaces, especially at the extruder mill of the mixer (> 90 rev/m3), the two-roll mill of mixers (> 70 rev/m3), mixer I loading (> 70 rev/m3), calendering (> 70 rev/m3) and fender vulcanizing (> 80 rev/m3) was even much more higher than that found in the urban indoor and outdoor air (2-9 rev/m3).(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity of the replica method in the detection of candidal infection among denture wearers with clinically healthy oral mucosa.

To ascertain the role of Candida in denture stomatitis, the practitioner must conduct a mycologic examination of the acrylic resin denture surface, because it acts as a reservoir for continuous reinfection of the palate. Twenty-two patients were examined to compare the sensitivity of the standard technique of swabbing the denture to that of a newly developed cast agar replica technique for detecting Candida albicans. The dentures were swabbed and cast replicas of the tissue-fitting surface of the dentures were made of both study populations. The majority of cultures obtained by swabbing failed to detect the presence of Candida albicans, while all cast agar replicas grew Candida albicans. The replica method for the detection of Candida albicans in edentulous patients seemed to be a more sensitive method than currently available mycologic methods.

Plaque accumulation on crowns made of various materials.

The rate of plaque accumulation on various materials used for fixed prostheses was investigated, and the composition of plaque formed on each surface was evaluated. Enamel, metal, acrylic resin, and porcelain surfaces were studied. Amounts of plaque that formed on the teeth and fixed restorations were scored using the method of Silness and Loe. Different individuals formed plaque at different rates, and the character and quantity of the plaque was different on the various materials. In a second study, acrylic resin, metal, and porcelain crowns were made for each of 10 patients. The amount of plaque absorbed onto each material after 1, 3, and 24 hours was recorded using scanning electron microscopy. The samples of dental plaque at 24 hours on each type of crown material were collected and investigated in a CHN Analyzer 184, revealing differences in the chemical composition of plaque adsorbed onto different surfaces. The results of SEM examination and biochemical analysis are presented.

An in vivo replica method for the site-specific detection of Candida albicans on the denture surface in denture stomatitis patients: correlation with clinical disease.

A site-specific agar replica technique for detecting Candida albicans on the acrylic resin denture surface of denture stomatitis patients has been developed. The method is selective for C. albicans during a finite incubation period with a specific synthetic growth medium. C. albicans colonies can be geographically observed on the replica and their presence can be correlated with inflammatory lesions visible on the mucosa of the maxillary and mandibular residual ridges. In 12 denture stomatitis patients studied, a close clinical correlation of Newton type III patients was noted but this clinical correlation could not be observed in Newton type I and II patients. In general, the number of C. albicans colonies increased with the severity of the inflammation. The findings are discussed in light of lack of knowledge of the etiology of the stomatitis. The importance of the replica method is also discussed.