Adsorption of clarithromycin on polystyrene nanoplastics surface and its combined adverse effect on serum albumin.

Emerging contaminants, such as antibiotics and nanoplastics, have garnered significant attention due to their potential adverse effects on diverse ecosystems. Antibiotic adsorption on the surface of nanoplastics potentially facilitates their long-range transport, leading to the synergistic effects of the complex. This research aims to examine the adsorption behavior of clarithromycin binding with polystyrene nanoplastics surface as well as their interaction between drug adsorbed polystyrene nanoplastics with serum albumin. Different spectroscopic methods were used to find out the interaction between clarithromycin and nanoplastics, under stimulated physiological conditions UV-vis spectroscopy showed a maximum of 22.8% percentage of the drug adsorbed with the polystyrene nanoplastics surface after 6 h of incubation. The fluorescence spectroscopic results demonstrated that the fluorescence intensity of serum albumin was quenched by the clarithromycin-polystyrene nanoplastics (CLA-PSNP) complex through static quenching. We calculated the number of binding stoichiometry, binding constants, and thermodynamic parameters. This study revealed that the CLA-PSNP binds to serum albumin spontaneously and its hydrophobic interactions played a significant role. The conformational changes in the structure of serum albumin were revealed from the findings of synchronous fluorescence spectra, CD spectra, and 3D fluorescence spectra, leading to the disturbance in functional activity. This study focuses valuable insights into the intermolecular interactions between clarithromycin-adsorbed polystyrene nanoplastics and serum albumin and its potential molecular-level biological toxicity.

Relationship between Rous sarcoma virus-induced expression of membrane antigen and phenotypic transformation.

Rous sarcoma virus-transformed hamster BHK fibroblasts express a virus-induced cell surface antigen undetectable in cells either transformed by unrelated viruses or infected by transformation-defective strains of Rous sarcoma virus. To clarify whether this antigen plays any role in the process of malignant transformation or is expressed at the cell surface only as a consequence of the acquisition of the transformed phenotype, we have investigated its expression at the cell surface of Rous sarcoma virus-transformed BHK cells treated with dibutyryl cyclic adenosine 3':5'-monophosphate and at the surface of parental BHK cells transiently transformed by the tumor promoter phorbol myristate acetate. In the dibutyryl cyclic adenosine 3':5'-monophosphate-treated cells, in which most of the parameters of the transformed phenotype are reverted to normality, but the product of the transforming gene is still present, virus-induced cell surface antigen is expressed. In the mirror experiment, this antigen is not expressed by phenotypically transformed but genetically normal phorbol myristate acetate-treated cells. It is concluded that the tumor membrane antigen studied is intimately associated with the expression of the function(s) controlled by the transforming gene.

DNA damage and cytotoxicity induced in mammalian cells by a tetramethylfuroquinolinone derivative.

1,4,6,8-Tetramethyl-2H-furo[2,3-h]quinolin-2-one [FQ] is an angelicin isoster characterized by a strong photosensitizing activity FQ shows a significant antiproliferative activity also in the dark, i.e., without UVA activation. The cytotoxic activity of FQ in the dark was detected in HeLa cells and in normal human lymphocytes; FQ showed notable antiproliferative effects, barely lower in comparison with ellipticine, used as a reference Similar results were obtained studying the FQ's capacity for forming chromosome aberrations. For both FQ and ellipticine, the chromosomal damage correlated closely with cell killing, when compared with ellipticine at the same levels of survival, FQ appeared to be much less genotoxic. Using alkaline elution we have investigated the ability of FQ to damage DNA. The formation of equivalent amounts of single-strand breaks (SSB) and DNA-protein cross-links (DPC) was observed; in addition, these lesions appeared to be located at the same sites in DNA. Experiments carried out with neutral elution demonstrated the formation of double-strand breaks (DSB). All these data are consistent with an inhibition of topoisomerase II; this hypothesis was confirmed performing an enzymatic test in vitro using topoisomerase II from Drosophila melanogaster embryos.

Lack of effect of glutathione depletion on cytotoxicity, mutagenicity and DNA damage produced by doxorubicin in cultured cells.

Since endogenous glutathione (GSH), the main non-protein intracellular thiol compound, is known to provide protection against reactive radical species, its depletion by diethylmaleate (DEM) was used to assess the role of free radical formation mediated by doxorubicin in DNA damage, cytotoxicity and mutagenicity of the anthracycline. Subtoxic concentrations of DEM that produced up to 75% depletion of GSH did not increase doxorubicin cytotoxicity in a variety of cell lines, including Chinese hamster ovary (CHO) and lung (V-79) cells, LoVo human carcinoma cells and P388 murine leukemia cells. Similarly, the number of doxorubicin-induced DNA single strand breaks in CHO cells and the mutation frequency in V-79 cells were not affected by GSH depletion. The results obtained suggest that mechanisms other than free radical formation are responsible for DNA damage, cytotoxicity and mutagenicity of anthracyclines.

Molecular interactions of ruthenium complexes in isolated mammalian nuclei and cytotoxicity on V79 cells in culture.

In this paper, the molecular interactions in isolated mammalian nuclei of three ruthenium complexes, which are putative antineoplastic chemotherapeutic agents effective in reducing metastatic tumours in vivo, have been investigated and compared with the well-known antitumour drug CDDP (cis-diamminedichloroplatinum). The compounds studied are: Natrans-RuCl4(DMSO)Imidazole (NAMI), Natrans-RuCl4(DMSO)Oxazole (NAOX) and Natrans-RuCl4(TMSO)- Isoquinoline (TEQU). This study shows that the drugs bind to DNA but induce few, if any, DNA interstrand crosslinks, which are considered as the main biological lesions involved in the cytotoxic activity of several already known antitumour drugs, whilst in the same experimental conditions, CDDP is confirmed to induce them. On the other hand, proteins appear to be an important target in the cell for these drugs, since proteins-DNA crosslinks are shown to be induced by the complexes. Moreover, we investigated Ru complexes for their direct cytotoxicity on V79 cells in culture, showing that two of them (NAMI and NAOX) do not significantly reduce the cloning efficiency of the cells even at concentrations as high as 2-3 mg/ml: only TEQU both reduces cloning efficiency and induces a significant number of mutants in V79 cells in culture.

Sodium butyrate affects the cytotoxic and mutagenic response of V79 Chinese hamster cells to the genotoxic agents, daunorubicin and U.V. radiation.

It has been suggested that conditions which lead to modifications in the chromatin structure could be responsible for an increased accessibility of DNA to genotoxic agents in eukaryotic cells. With this in mind, the cytotoxic and mutagenic activity of the anthracycline antibiotic, daunorubicin, and of UV radiation was assayed on V79 Chinese hamster cells pretreated or not with 5 mM sodium butyrate, an agent known to induce modifications in the chromatin structure: this treatment in fact proved to induce the hyperacetylation of the core histones, and moreover to enhance the cytotoxic response of the cells to both daunorubicin and UV radiation and the mutagenic response to daunorubicin.

Mutagenic activity of 3 diazoacetylglycine derivatives on V79 Chinese hamster cells.

3 diazoacetylglycine derivatives, diazoacetylglycine amide (DGA), diazoacetylglycine ethyl ester (DGE) and diazoacetylglycine hydrazide (DGH), known as antitumour agents, and shown to be mutagenic in bacteria, were studied for their mutagenic activity in the HGPRT system of V79 Chinese hamster cells in culture (V79/HGPRT system). All 3 drugs were highly effective in inducing 6-thioguanine-resistant mutants at concentrations that were not significantly cytotoxic.

DNA damage and topoisomerase II inhibition induced by a benzopsoralen derivative.

The ability of 4-hydroxymethyl-4',5'-benzopsoralen (HMBP) to damage DNA of Chinese hamster ovary cells (CHO) and to inhibit the activity of topoisomerase II in vitro has been studied. This compound is characterized by a fourth ring condensed at the furan-side in the psoralen molecule. Contrary to other known furocoumarin derivatives, HMBP induces chromosomal aberrations in mammalian cells without UVA activation. The lesions induced in the dark by HMBP in DNA were studied by alkaline and neutral elution in CHO cells; comparable amounts of single-strand breaks and DNA-protein cross-links as well as the formation of double-strand breaks were detected. Moreover, HMBP appeared to inhibit the activity of mammalian topoisomerase II in vitro, in both the catenation and the decatenation assay. In these experiments the drug was effective only when it was pre-incubated with DNA substrate. These results are also consistent with the cytotoxic and mutagenic activity of HMBP in the dark, as tested on V79 Chinese hamster cells (V79/HGPRT system).

Mutagenic activity of four furocoumarins: angelicin, 4,5'-dimethyl-angelicin, psoralen and 8-methyl-psoralen on V79 Chinese hamster cells.

Four furocoumarins, two having a linear structure (psoralen and 8-methyl-psoralen) and two having an angular structure (angelicin and 4,5'-dimethyl-angelicin), were studied for their mutagenic activity in the HGPRT system on V79 chinese hamster cells in culture (V79/HGPRT system). All the four drugs, when activated by near-ultraviolet (NUV) light, were effective in inducing HGPRT mutants. Their efficiency ranked in the following order: 8-methyl-psoralen greater than psoralen = 4,5-dimethylangelicin greater than angelicin.

Darier's disease: a calcium-signaling perspective.

Ca(2+) influx evoked across the plasma membrane upon internal store depletion is essential for a myriad of cellular functions including gene expression, cell proliferation, differentiation and even apoptosis. Darier's disease (DD), an autosomal dominant inherited disorder of the skin, arising due to mutations in the isoform 2 of the sarco (endo) plasmic reticulum Ca(2+) ATPase (SERCA2), exemplifies an anomaly of Ca(2+) signaling disturbances. Owing to loss of function mutations in SERCA2, keratinocytes in DD patients have a reduced pool of endoplasmic reticulum (ER) Ca(2+). Importantly, the status of ER Ca(2+) is critical for the activation of a class of plasma membrane Ca(2+) channels referred to as store operated Ca(2+) channels (SOCs). The widely expressed transient receptor potential (TRP) family of channels is proposed to be SOCs. In this review we discuss DD from the viewpoint of Ca(2+) signaling and present a potential role for TRPC1 in the disease pathogenesis.

The child-rearing attitudes of the parents of (male and female) schizophrenics.

It was hypothesised that there exists significant difference between the parents of male and of female schizophrenics and those of the corresponding control group, in the child-rearing attitudes. The experimental group consisted of the 62 pairs of parents of 62 male and 38 pairs of parents of 38 female schizophrenics. A control group of 100 pairs of parents of mentally and physically healthy off-springs were taken. Subjects were matched for intelligence, age, sex, level of education, religion and per capita income and all of them were free from mental illness at any time during their life. The Bengali version of PARI for fathers were used. The results were consistent with the hypotheses. Certain child-rearing attitudes of the parents of schizophrenics were found which were significantly different from the corresponding control groups.

HMG proteins released from the chromatin following incubation of mammalian nuclei with ethidium bromide.

The low-molecular-mass high-mobility group (HMG) chromosomal proteins, namely HMG-14, HMG-17, and HMG-I, which have been found in several proliferating tissues, are released following incubation of nuclei isolated from young rat thymus and from human placenta in a low ionic strength medium containing the intercalating agent ethidium bromide. The amount of HMG proteins released is drug concentration-dependent, but at very high concentrations (20-40 mM) other low- and high-molecular-mass proteins, and even histones, are released. These results suggest a very weak interaction of the HMG proteins with DNA, so that they can be easily detached from the chromatin as a consequence of the interaction of DNA with the intercalating agent.

Mechanically induced ATP release from human osteoblastic cells.

Extracellular ATP is a widespread autocrine/paracrine signal since many animal cells release ATP in the extracellular medium; often this release is mechanosensitive, but the molecular mechanism is still unclear. The involvement of vesicular release, conductive channels, or ABC transporters has been suggested in different cell types. We investigated the mechanism of ATP release in human HOBIT osteoblastic cells, in which mechanical stimulation induced intercellular calcium waves sustained by both cell-to-cell coupling through gap junctions and ATP release. In this study we employed a luciferin-luciferase bioluminescence assay to measure the amount of ATP released under different stimulatory conditions. Given the role of connexin hemichannels in favoring passive NAD(+) transport [Bruzzone, S., et al. (2001) FASEB J. 15, 10-12], the involvement of connexin hemichannels as putative ATP transporters was initially investigated. In HOBIT cells overexpressing connexin43 the amount of nucleotide released under basal and stimulated conditions was similar to non-transfected cells, ruling out a major involvement of connexin hemichannels in ATP transport. In nontransfected HOBIT cells mechanical stimulations induced by medium displacement and hypotonic stress consistently enhanced ATP efflux. Cytochalsin D treatment did not alter basal and stimulated ATP release, while elevated cAMP levels consistently reduced efflux in both cases. ATP released by hypotonic stress and medium displacement evoked intracellular Ca(2+) transients in fura2-loaded HOBIT cells, indicating that different mechanical stimuli activate physiological cell responses.

Solid-state laser pumping with a planar compound parabolic concentrator.

A novel solid-state laser-pumping scheme is proposed that combines a reflective lamp chamber and a compound parabolic concentrator (CPC) as a light guide. The CPC is made of a transparent material of high refractive index, and light is guided by the total internal reflection, with drastically reduced reflection losses. Material is chosen so that the absorption losses are minimized in the pumping wavelength range. The lamp chamber is designed with the principles of nonimaging optics, which ensures that the radiation is efficiently transferred from the lamp to the input aperture of the CPC. The pumping efficiency was first estimated theoretically, which gave us enough justification for the more accurate calculations with ray tracing. Single as well as multiple pumping cavities are discussed. New pumping geometry results in significantly increased pumping efficiency compared with conventional geometries. Also the lamp and the laser rod are separated, leading to reduced thermal load. We found that the proposed pumping method is also applicable to diode-pumped lasers.

Effect of excision repair system on antibacterial and mutagenic activity of daunomycin and other intercalating agents in Salmonella typhimurium.

Daunomycin and adriamycin, are more mutagenic and antibacterial for a strain of Salmonella typhimurium defective for the uvrB gene than for its uvr+ counterpart. Other intercalating agents, as some acridine dyes, affect equally the two bacterial strains.

Butyrate effect on nuclear proteins of two Chinese hamster cell lines.

The effect of sodium butyrate on the nuclear proteins of two Chinese hamster cell lines (V79 and CHO) was studied. Butyrate treatment induces hyperacetylation of core histones in both cell lines, while H1 histone shows a different behavior. In CHO cells H1 is dephosphorylated following butyrate incubation; V79 do not show any change of H1 subtypes. It seems that H1 response to butyrate treatment is cell type dependent. Using silver staining a group of proteins that could be present in vivo in the nucleo-protein complex was also detected.

Genotoxic activity of some water-soluble derivatives of 5-methoxypsoralen and 8-methoxypsoralen.

This paper shows some results obtained by assaying the genotoxic activity on procaryotic and eucaryotic cells of some water-soluble psoralen derivatives. In particular, six newly synthesized derivatives of 5-methoxypsoralen (5-MOP) and of 8-methoxypsoralen (8-MOP) were tested; in previous studies they showed a strong anti-proliferative activity and a slight phototoxic effect; moreover, in view of a clinical use in the therapy of hyperproliferative skin diseases, these drugs should be less toxic than their parent compounds because of their good water solubility which could lead to a more efficient absorption and excretion. All the compounds tested here have shown genotoxic activity on both procaryotic and eucaryotic systems: however, on the procaryotic cells the water-soluble derivatives were less genotoxic than their respective parent compounds 5-MOP and 8-MOP. Quite different results were obtained on V79 Chinese hamster cells, showing that, in general, the 8-methoxy-derivatives are more mutagenic than the methoxy-ones, although the 5-MOP itself was shown to be highly genotoxic in this system. This fact confirms that a conclusive estimate of the genotoxic risk related to the use of new drugs cannot be drawn from the results obtained on a single biological system.

In vitro mutagenic activity of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) in eukaryotic and prokaryotic cells.

The in vitro mutagenic activity of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC), has been studied in bacteria and Chinese hamster cells with and without metabolic activation by rat liver microsomes. DTIC was found to be highly mutagenic in the two systems. It is noteworthy that DTIC in the prokaryotic systems did not require metabolic activation to be effective. By comparing the mutagenic activity on bacteria of DTIC and of its monomethyl-and hydroxy-methyl-derivatives (MIC and HMIC), it is evident that MIC and HMIC display a pattern of mutagenicity different from DTIC. It suggests that neither MIC nor HMIC are the direct responsible metabolites for the mutagenic activity of DTIC in bacteria.