Biomedical subjects

A Seidel

Publications and source records attributed to A Seidel.

At least 73 records · Page 4Linked to original sources

PubMed1998

Erratum to "23Na solid state MAS NMR of sodium halides occluded in zeolites".

Occlusion of sodium chloride and sodium bromide in zeolitic pores was performed by heating mixtures of the salts with zeolites NaY and NaA under high vacuum conditions. The obtained samples were subjected to various further pretreatments like washing with water and zinc-exchange, and were investigated spectroscopically with the 23Na MAS NMR technique at various Zeeman field strengths. In the case of NaY, the halides are occluded in both types of cages of the faujasite structure. About 90% of the sodalite cages are shown to have incorporated salt which is concluded to be part of [Na4Hal]3+ clusters as in the case of sodalite type materials.

Bromides↗

PubMed1997

Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[a,l]pyrene or its diol epoxides.

Polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants, and some are potent carcinogens in rodents. Carcinogenic PAH are activated in cells to metabolites that react with DNA to form stable covalent DNA adducts. It has been proposed [Cavalieri, E. L. & Roger, E. G. (1995) Xenobiotica 25, 677-688] that unstable DNA adducts are also formed and that apurinic sites in the DNA resulting from unstable PAH adducts play a key role in the initiation of cancer. The potent carcinogen dibenzo[a,l]pyrene (DB[a, l]P) is activated in cells to (+)-syn- and (-)-anti-DB[a,l]P-11, 12-diol-13,14-epoxide (DB[a,l]PDE), which have been shown to form stable adducts with DNA. To evaluate the importance of unstable PAH adducts, we compared stable adduct formation to apurinic site formation. Stable DB[a,l]PDE adducts were determined by 33P-postlabeling and HPLC. To measure apurinic sites they were converted to strand breaks, and these were monitored by examining the integrity of a particular restriction fragment of the dihydrofolate reductase gene. The method easily detected apurinic sites resulting from methylation by treatment of cells or DNA with dimethyl sulfate or from reaction of DNA with DB[a,l]P in the presence of horseradish peroxidase. We estimate the method could detect 0.1 apurinic site in the 14-kb fragment examined. However, apurinic sites were below our limit of detection in DNA treated directly with (+)-syn- or (-)-anti-DB[a,l]PDE or in DNA from Chinese hamster ovary B11 cells so treated, although in these samples the frequency of stable adducts ranged from 3 to 10 per 14 kb. We also treated the human mammary carcinoma cell line MCF-7 with DB[a,l]P and again could not detect significant amounts of unstable adducts. These results indicate that the proportion of stable adducts formed by DB[a,l]P activated in cells and its diol epoxides is greater than 99% and suggest a predominant role for stable DNA adducts in the carcinogenic activity of DB[a,l]P.

Animals↗

PubMed1997

Decreased drug accumulation in a mitoxantrone-resistant gastric carcinoma cell line in the absence of P-glycoprotein.

An established gastric-carcinoma cell line, EPG85-257P, is extremely sensitive to mitoxantrone (IC50, 0.12 ng/ml). Stepwise selection with mitoxantrone for 3 years resulted in a cell line (EPG85-257RN) that is 7,056-fold resistant to mitoxantrone (IC50, 846 ng/ml) and displays cross-resistance to the topoisomerase(topo)-II poisons ametantrone (411x), etoposide (112x) and teniposide (60x) as well as the topo-I poisons 7-ethyl-10-hydroxycamptothecin (331x) and topotecan (58x). We now show that this resistance is multifactorial. Western blotting revealed a 5-fold decrease in topo-IIalpha polypeptide in the mitoxantrone-resistant cells. Immunohistochemistry and Western blotting failed to demonstrate P-glycoprotein overexpression. Formation of trapped topo-II-DNA complexes in the resistant cells required higher mitoxantrone concentrations than in parental cells, even though nuclei isolated from the EPG85-257RN cells formed cleavage complexes normally. In agreement with these observations, which suggest the possibility of a defect in mitoxantrone accumulation, examination of mitoxantrone accumulation in both cell lines by confocal laser microscopy revealed that the EPG85-257RN cells accumulate less mitoxantrone at steady state. From these results, we propose that mitoxantrone accumulation, along with alterations in topo-IIalpha expression, contribute to the resistance to mitoxantrone observed in these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.

We have shown that the oval cell line OC/CDE 22 can be transformed by the highly carcinogenic fjord-region diol epoxides of benzo[c]phenanthrene. Mutational activation of the ras proto-oncogene family has been proposed to be a critical event in the formation of tumors induced by polycyclic aromatic hydrocarbons. Therefore, we investigated whether in the earlier transformed OC/CDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OC/CDE 22 cells by the 4 stereoisomeric benzo[c]phenanthrene diol epoxides in vitro is independent of activation of the Ha-ras proto-oncogene. In addition, Northern and Western blot analyses revealed no overexpression of the Ha-ras protooncogene in the transformed OC/CDE 22 cell lines. However, transfection of the OC/CDE 22 cells with an activated Ha-ras oncogene malignantly transformed the OC/CDE 22 cells, and the transfected cells served as precursor cells of tumors with a cholangiocellular morphology and phenotype. Our latter finding reinforces the view that OC/CDE 22 cells are committed to the bile duct epithelial cell lineage.

Animals↗

PubMed1997

A comparative investigation of DNA adducts, DNA strand breaks and gene mutations induced by benzo[a]pyrene and (+/-)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide in cultured human cells.

Genotoxic effects of benzo[a]pyrene (BP) and its reactive metabolites (+/-)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide ((+/-)-anti-BPDE) were comparatively investigated in vitro with the permanent human fibroblast cell line MRC5CV1. Induced DNA adducts were measured by 32P-postlabeling, DNA strand breakage was determined by the comet assay and the HPRT gene mutation test was used to detect cytotoxicity and mutagenicity. Treatment of MRC5CV1 cells with S9 mix-activated BP or with (+/-)-anti-BPDE resulted in a concentration-dependent increase in DNA adducts and strand breaks. Genotoxic effects of BP and (+/-)-anti-BPDE were detected by 32P-postlabeling and the comet assay with similar sensitivity. However, under the same experimental conditions, a clear induction of gene mutations was only found after (+/-)-anti-BPDE treatment. The relationship between the induction of primary DNA alterations like DNA strand breaks and DNA adducts and the induction of gene mutations is discussed.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1997

Visualization of a covalent intermediate between microsomal epoxide hydrolase, but not cholesterol epoxide hydrolase, and their substrates.

Mammalian soluble and microsomal epoxide hydrolases have been proposed to belong to the family of alpha/beta-hydrolase-fold enzymes. These enzymes hydrolyse their substrates by a catalytic triad, with the first step of the enzymatic reaction being the formation of a covalent enzyme-substrate ester. In the present paper, we describe the direct visualization of the ester formation between rat microsomal epoxide hydrolase and its substrate. Microsomal epoxide hydrolase was precipitated with acetone after brief incubation with [1-(14)C]epoxystearic acid. After denaturing SDS gel electrophoresis the protein-bound radioactivity was detected by fluorography. Pure epoxide hydrolase and crude microsomes showed a single radioactive signal of the expected molecular mass that could be suppressed by inclusion of the competitive inhibitor 1,1,1-trichloropropene oxide in the incubation mixture. In a similar manner, 4-fluorochalcone-oxide-sensitive binding of epoxystearic acid to rat soluble epoxide hydrolase could be demonstrated in rat liver cytosol. Under similar conditions, no covalent binding of [26-(14)C]cholesterol-5alpha,6alpha-epoxide to microsomal proteins or solubilized fractions tenfold enriched in cholesterol epoxide hydrolase activity could be observed. Our data provide definitive proof for the formation of an enzyme-substrate-ester intermediate formed in the course of epoxide hydrolysis by microsomal epoxide hydrolase, show no formation of a covalent intermediate between cholesterol epoxide hydrolase and its substrate under the same conditions as those under which an intermediate was shown for both microsomal and soluble epoxide hydrolases and therefore indicate that the cholesterol epoxide hydrolase apparently does not act by a similar mechanism and is probably not structurally related to microsomal and soluble epoxide hydrolases.

Amino Acid Sequence↗

PubMed1997

23Na solid state MAS NMR of sodium halides occluded in zeolites.

Bromides↗

PubMed1997

Conformational studies of stereoisomeric tetrols derived from syn- and anti-dibenzo[a,l]pyrene diol epoxides.

An understanding of the conformational behavior of the stereoisomeric tetrols at the 11,12,13,14-positions of dibenzo[a,l]pyrene (DB[a,l]P) is essential for the spectroscopic identification of DNA adducts derived from the biologically highly active fjord region syn- and anti-DB[a,l]P-11,12-diol 13,14-epoxides. Conformational effects are expected to play an important role in DNA-DB[a,l]P diol epoxide reactivity, base-sequence specificity, and conformation dependent repair. The results of conformational studies on trans-anti-, cis-anti-, and cis-syn-DB[a,l]P tetrol isomers are presented and compared to the results obtained previously for trans-syn-DB[a,l]P tetrol (Carcinogenesis 17, 829-837, 1996). Molecular mechanics, dynamical simulations, and semiempirical calculations of electronic transitions are used to interpret the low-temperature fluorescence spectra and 1H NMR data. Molecular dynamics simulations (in vacuo) identified two conformers (I and II) for each of the tetrol isomers; in all conformations the aromatic ring system is severely distorted. Fluorescence line-narrowing (FLN) spectroscopy identified two distinct conformational species for the trans-anti isomer, one occurring in ethanol and the other occurring in a glycerol/water matrix. The corresponding structures are assigned based on the S1<--S0 transition energies calculated for conformers I and II, respectively. 1H NMR spectroscopy confirmed the structure of conformer I at room temperature. In contrast to trans-syn-DB[a,l]P tetrol (where the major conformation was identified as a boat structure), both conformations of trans-anti-DB[a,l]P tetrol feature a half-chair structure for the cyclohexenyl ring with different orientations of the hydroxyl groups. For cis-anti- and cis-syn-DB[a,l]P tetrols, only a single conformer is detected by FLN spectroscopy. The NMR results for the latter appear to be most consistent with a mixture of two half-chair conformers I and II, while for the cis-anti isomer a flattened, boatlike conformation was observed. The generally good agreement between the NMR coupling constants and those estimated theoretically indicates that these structures should serve as good starting points for spectroscopic or computational studies of DNA adducts derived from DB[a,l]P diol epoxides.

Benzopyrenes↗

PubMed1997

Metabolic activation of the (+)-S,S- and (-)-R,R-enantiomers of trans-11,12-dihydroxy-11,12-dihydrodibenzo[a,l]pyrene: stereoselectivity, DNA adduct formation, and mutagenicity in Chinese hamster V79 cells.

Polycyclic aromatic hydrocarbons require metabolic activation in order to exert their biological activity initiated by DNA binding. The metabolic pathway leading to bay or fjord region dihydrodiol epoxides as ultimate mutagenic and/or carcinogenic metabolites is thought to play a dominant role. For dibenzo[a,l]pyrene, considered as the most potent carcinogenic polycyclic aromatic hydrocarbon, the formation of the fjord region syn- and/or anti-11,12-dihydrodiol 13,-14-epoxide (DB[a,l]PDE) diastereomers has been found to be the principal metabolic activation pathway in cell cultures leading to DNA adducts. In order to further elucidate the stereoselectivity involved in this activation pathway via the formation of the trans-11,12-dihydrodiol, we have synthesized the enantiomerically pure 11,12-dihydrodiols of dibenzo[a,l]-pyrene and investigated their biotransformation in rodents. Incubations with liver microsomes of Sprague-Dawley rats and CD-1 mice pretreated with Aroclor 1254 revealed that the enzymatic conversion to the fjord region DB[a,l]PDE strongly depends on the absolute configuration of the 11,12-dihydrodiol enantiomers. While oxidation at the 13,14-position of the (+)-(11S,12S)-dihydrodiol is limited to a small extent, the (-)-11R,12R-enantiomer is metabolized to its fjord region dihydrodiol epoxides in considerably higher amounts. Moreover, this substrate is transformed with high stereoselectivity to the corresponding (-)-anti-dihydrodiol epoxide by liver microsomes of Aroclor 1254-treated rodents. The metabolism results were in good accordance with the extent of stable adduct formation in calf thymus DNA as investigated by the 32P-postlabeling technique and with the mutagenicity in Chinese hamster V79 cells of the two enantiomeric 11,12-dihydrodiols mediated by hepatic postmitochondrial preparations of Aroclor 1254-treated rats. The results indicate that both genotoxic events occurred predominantly by the stereoselective activation of the (-)-(11R,12R)-dihydrodiol to the (-)-anti-DB[a,l]PDE with R,S,S,R-configuration.

Animals↗

PubMed1997

Stereoselective activation of dibenzo[a,l]pyrene and its trans-11,12-dihydrodiol to fjord region 11,12-diol 13,14-epoxides in a human mammary carcinoma MCF-7 cell-mediated V79 cell mutation assay.

Dibenzo[a,l]pyrene (DB[a,l]P) represents the most potent carcinogenic polycyclic aromatic hydrocarbon (PAH) yet discovered. Like other PAHs, DB[a,l]P requires metabolic activation to exert its mutagenic and/or carcinogenic activity. In the human mammary carcinoma cell line MCF-7, DB[a,l]P is stereoselectively metabolized to the (-)-anti- and (+)-syn-DB[a,l]P-11,12-diol 13,14-epoxides (DB[a,l]PDE) which both bind extensively to deoxyadenosine residues in DNA. To further characterize the underlying mechanism of its strong carcinogenicity, the relationship between DNA binding and mutagenicity of DB[a,l]P was determined. Racemic DB[a,l]P-11,12-dihydrodiol and the two individual (+)- and (-)-enantiomers, the metabolic precursors of the stereoisomeric fjord region dihydrodiol epoxides, were also investigated. Induction of mutations at the HPRT locus was measured in a MCF-7 cell-mediated Chinese hamster V79 cell mutation assay. The parent hydrocarbon, (+/-)-DB[a,l]P-11,12-dihydrodiol, and (-)-DB[a,l]P-11,12-dihydrodiol were highly mutagenic under the assay conditions. In contrast, (+)-DB[a,l]P-(11S,12S)-dihydrodiol was not mutagenic using MCF-7 cells as the metabolic activating system. Analysis of DNA adducts in the same experiments revealed that MCF-7 cells treated with (-)-DB[a,l]P-11,12-dihydrodiol formed exclusively (-)-anti-DB[a,l]-PDE adducts whereas cells treated with (+)-DB[a,l]P-11,12-dihydrodiol did not contain detectable levels of DNA adducts. These results suggest that specific cytochrome P450 enzymes may have high stereoselectivity for activation of the two DB[a,l]P-11,12-dihydrodiol enantiomers, and this may play an important role in the metabolic activation of the strong carcinogen DB[a,l]P in human cells.

Animals↗

PubMed1997

Glutathione conjugation of bay- and fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferases M1-1 and P1-1.

Metabolism of polycyclic aromatic hydrocarbons in mammalian cells results in the formation of vicinal diol epoxides considered as ultimate carcinogens if the oxirane ring is located in a bay- or fjord-region of the parent compound. In the present study, individual stereoisomers of the bay-region diol epoxides of chrysene, dibenz[a,h]anthracene, and benzo[a]pyrene as well as of the fjord-region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene, and benzo[g]-chrysene have been incubated with GSH in the presence of human glutathione transferases GSTM1-1 (a mu-class enzyme) and GSTP1-1 (a pi-class enzyme). As previously shown with GSTA1-1 (an alpha-class enzyme) both M1-1 and P1-1 demonstrate considerable activity toward a number of the diol epoxides studied, although a great variation in catalytic efficiency and enantioselectivity was observed. With GSTM1-1, the bay-region diol epoxides, in particular the syn-diastereomers were in most cases more efficiently conjugated with GSH than the fjord-region analogues. GSTM1-1 demonstrated an enantioselectivity ranging from no preference (50%) to high preference (> or = 90%) for conjugation of the enantiomers with R-configuration at the benzylic position of the oxirane ring. With GSTP1-1, the enzyme demonstrated appreciable activity toward both bay- and fjord-region diol epoxides and, in most cases, a preference for the anti-diastereomers. In contrast to GSTM1-1 and as previously shown for GSTA1-1, GSTP1-1 showed an exclusive preference for conjugation of the enantiomers with R-configuration at the benzylic oxirane carbon. With both GSTM1-1 and GSTP1-1, the chemically most reactive diol epoxide, the (+)-syn-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,-10-tetrahydrobenzo[a]pyrene (BPDE), was the best substrate. As for GSTA1-1, no obvious correlation between chemical reactivity or lipophilicity of the compounds and catalytic efficiencies was observed. Molecular modeling of diol epoxides in the active sites of GSTP1-1 and -A1-1 is in agreement with the assumption, based on functional studies, that the H-site of GSTA1-1 [Jernström et al. (1996) Carcinogenesis 17, 1491-1498] can accommodate stereoisomers of different sizes. Further, modeling of the enantiomers of anti- and syn-BPDE in the active site of GSTP1-1 provides an explanation for the exclusive preference for the enantiomers with R-configuration at the benzylic oxirane carbon. These isomers could be snuggly fitted in the H-site close to the GSH sulfur, whereas those with opposite stereochemistry could not.

Bay-Region, Polycyclic Aromatic Hydrocarbon↗

PubMed1997

Covalent DNA adducts formed by benzo[c]chrysene in mouse epidermis and by benzo[c]chrysene fjord-region diol epoxides reacted with DNA and polynucleotides.

The metabolic activation in mouse skin of benzo[c]chrysene (B[c]C), a weakly carcinogenic polycyclic aromatic hydrocarbon (PAH) present in coal tar and crude oil, was investigated. Male Parkes mice were treated topically with 0.5 mumol of B[c]C, and DNA was isolated from the treated areas of skin at various times after treatment and analyzed by 32P-postlabeling. Seven adduct spots were detected, at a maximum level of 0.89 fmol of adducts/microgram of DNA. Four B[c]C-DNA adducts persisted in skin for at least 3 weeks. Treatment of mice with 0.5 mumol of the optically pure putative proximate carcinogens (+)- and (-)-trans-benzo[c]chrysene-9,10-dihydrodiols [(+)- and (-)-B[c]C-diols] led to the formation of adducts which comigrated on TLC and HPLC with some of those formed in B[c]C-treated mice. The major adduct formed in mouse skin treated with B[c]C coeluted on TLC and HPLC with an adduct formed in mouse skin treated with (-)-B[c]C-diol. These results suggested that the detected adducts were formed by the fjord-region B[c]C-9,10-dihydrodiol 11,12-epoxides (B[c]CDEs). To test this, the four optically pure synthetic B[c]CDEs were reacted in vitro with DNA and with synthetic polynucleotides and these samples were 32P-postlabeled. Cochromatography, both on TLC and HPLC, of in vitro and in vivo adducts indicated that B[c]C is activated in mouse skin through formation of the (-)-anti- and (+)-syn-B[c]CDE with 9R,10S,11S,12R- and 9S,10R,11S,12R- absolute configuration, respectively, both of which formed two DNA adducts in vivo. However, the major adduct present in the B[c]C-treated skin DNA was not a fjord-region B[c]CDE adduct but was possibly derived from a bay region B[c]CDE at the 1,2,3,4-position. The extent of DNA adduct formation by B[c]C in mouse skin DNA was lower than that of moderately carcinogenic PAHs previously studied by this method, suggesting a correlation between extent of DNA adduct formation and carcinogenic potential.

Animals↗

PubMed1997

Structure-activity relationship in the induction of chromosomal aberrations and spindle disturbances in Chinese hamster epithelial liver cells by regioisomeric phenanthrene quinones.

Four regioisomeric phenanthrene (PH) quinones (Q) were investigated for their ability to induce chromosomal damage and spindle disturbances. PH 1,4-Q and PH 1,2-Q induced structural as well as numerical chromosomal aberrations, whereas the isomers PH 9,10-Q and PH 3,4-Q were virtually inactive in this respect, However, all four compounds enhanced the frequency of c-mitoses.

Animals↗

PubMed1997

Detection of human topoisomerase II alpha in cell lines and tissues: characterization of five novel monoclonal antibodies.

We report five novel monoclonal antibodies (Ki-S1, Ki-S4, Ki-S6, Ki-S7, and Ki-S8) reactive with a proliferation-related nuclear antigen. In immunoprecipitation and Western blot experiments using crude nuclear extracts, they recognized a protein of 170 kD that, after proteolytic digestion of the immunoprecipitate and sequencing of the resulting peptides, was identified as the alpha-isoform of human topoisomerase II. This was confirmed by testing the antibodies on a highly purified enzyme preparation. Crossreactivity with topoisomerase II beta was ruled out by testing the antibodies on crude extracts from yeast cells expressing the beta-isoform exclusively. The antibodies bind the antigen with different affinities and at different epitopes, apparently located within the carboxyl third of the enzyme. All five antibodies are suitable for archival material after adequate antigen retrieval, thereby enabling retrospective studies. This report illustrates the tissue and subcellular distribution of the antigen through the cell cycle by immunohistochemistry and confocal fluorescence microscopy. The antibodies will be useful tools in further analysis of morphological and functional aspects of topoisomerase II and may serve diagnostic purposes, as well as providing prognostic information in tumor pathology.

Antibodies, Monoclonal↗

PubMed1997

[Studies on mutagenicity of polycyclic aromatic hydrocarbon-DNA adduct].

Mutagenic effect of polycyclic aromatic hydrocarbon (PAH)-DNA adduct was studied to explore mechanism of carcinogenecity of PAH. Adduct was formed by chemical group protection and nucleophilic displacement methods with modification of deoxyadenosine by PAH-dihydrodiol epoxide. Partial analogous sequence of human protooncogene ras (H-ras) containing mutagenic hotspot 61 codon (CAG) was synthesized by a DNA assembler and DNA was duplicated with a template of partial analogous sequence containing adduct protooncogene. Results showed that PAH-DNA adduct could obviously affect the process of DNA duplication, cause interruption of duplication of DNA or translesional bypass, lower fidelity of duplication, and induce misincorporation of bases in corresponding locus of the adduct, with point mutation of transversion (from A-T to T-A).

DNA Adducts↗

PubMed1996

Increased CD56+ natural killer cells and related cytokines in major depression.

Twenty-seven inpatients with major depression were examined four times within 6 weeks to assess CD56+ natural killer (NK) cell counts by flow cytometry and to assess the related lymphokines interleukin-2 and interferon-gamma in a whole blood assay after mitogen stimulation with phytohemagglutinin (PHA). The patient showed significantly higher counts of the fraction of 56+ NK cells and a greater lymphokine response to PHA than the controls. A significant correlation between lymphokine secretion and CD56+ cell counts was detected in the patients' acute clinical stage, but not in healthy controls or in patients after clinical improvement.

Adult↗

PubMed1996

Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis.

The single cell gel test (SCG-test or comet assay) is a rapid and sensitive method for measuring DNA damage and repair in individual cells. A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations. We are therefore investigating in a cell culture system with human cells (MRC5CV1) the induction of DNA damage by environmental mutagens and the formation of mutations at the HPRT gene. In the present study we investigated benzo[a]pyrene (BP), an environmental mutagenic and carcinogenic polycyclic aromatic hydrocarbon, and its reactive metabolite (+)-anti-benzo[a]pyrene-7,8-diol 9, 10-oxide ((+)-anti-BPDE). S9 mix activated BP and the direct acting mutagen (+)-anti-BPDE caused a concentration-related increase in DNA migration in the comet assay. Postincubation experiments indicated that induced DNA effects are eliminated by DNA repair within 24 h. BP-treatment caused a strong genotoxic effect in the comet assay but had only a marginal effect on the frequency of gene mutations. When cells were treated with BP in the presence of cadmium sulphate, a clear increase in genotoxicity was observed while the effect on mutations was unchanged. Our results indicate that DNA alterations detected with the comet assay do not necessarily relate to mutagenesis. The absence of a close relationship between DNA migration in the comet assay and mutagenesis may be explained by the fact that some effects seen in the comet assay occur as a consequence of an error free DNA repair process.

Benzo(a)pyrene↗

PubMed1996

Comparison of immunological effects of Fullerene C60 and raw soot from Fullerene production on alveolar macrophages and macrophage like cells in vitro.

Two carbon modifications, C60 and Raw Soot (RS) from fullerene production, were incubated with macrophages and macrophage-like cells. Their effects were compared both to DQ12 Quartz as a positive particle control known to damage BAM and HL60M, and LPS or zymosan as biological inducers of immunological reactions. C60 as well as RS are not cytotoxic as compared to DQ12. C60 seems to induce a lower chemotactic activity than RS and DQ12. Furthermore, C60 is of no or only very little influence on the formation of reactive oxygen species (ROS). RS itself is oxidatively active both with H2DFC-DA in in vitro cell culture and with KMB in a cell free incubation under the influence of light. It is not yet clear whether the in vitro effects of RS are caused by ROS formation by the cells and/or the oxidative activity due to light as indicated from the results with KMB.

Acetylglucosaminidase↗