Progressive effects of silver nanoparticles on hormonal regulation of reproduction in male rats.

The growing use of silver nanoparticles (AgNPs) in various applications, including consumer, agriculture and medicine products, has raised many concerns about the potential risks of nanoparticles (NPs) to human health and the environment. An increasing body of evidence suggests that AgNPs may have adverse effects of humans, thus the aim of this study was to investigate the effects of AgNPs on the male reproductive system. Silver particles (20nm AgNPs (groups Ag I and Ag II) and 200nm Ag sub-micron particles (SPs) (group Ag III)) were administered intravenously to male Wistar rats at a dose of 5 (groups Ag I and Ag III) or 10 (group Ag II) mg/kg of body weight. The biological material was sampled 24h, 7days and 28days after injection. The obtained results revealed that the AgNPs had altered the luteinising hormone concentration in the plasma and the sex hormone concentration in the plasma and testes. Plasma and intratesticular levels of testosterone and dihydrotestosterone were significantly decreased both 7 and 28days after treatment. No change in the prolactin and sex hormone-binding globulin concentration was observed. Exposure of the animals to AgNPs resulted in a considerable decrease in 5α-reductase type 1 and the aromatase protein level in the testis. Additionally, expression analysis of genes involved in steroidogenesis and the steroids metabolism revealed significant down-regulation of Star, Cyp11a1, Hsd3b1, Hsd17b3 and Srd5a1 mRNAs in AgNPs/AgSPs-exposed animals. The present study demonstrates the potential adverse effect on the hormonal regulation of the male reproductive function following AgNP/AgSP administration, in particular alterations of the sex steroid balance and expression of genes involved in steroidogenesis and the steroids metabolism.

Time-dependent biodistribution and excretion of silver nanoparticles in male Wistar rats.

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles owing to their antimicrobial properties. The motivation of the present study was (1) to analyze the effect of silver particle size on rat tissue distribution at different time points, (2) to determine the accumulation of AgNPs in potential rat target organs, (3) to analyze the intracellular distribution of AgNPs and (4) to examine the excretion of AgNPs by urine and feces. AgNPs were characterized by dynamic light scattering (DLS), zeta potential measurements, BET surface area measurements, transmission and scanning electron microscopy. AgNPs (20 and 200 nm) were administered intravenously (i.v.) to male Wistar rats at a dose of 5 mg kg(-1) of body weight. Biological material was sampled 24 h, 7 and 28 days after injection. Using inductively coupled plasma-mass spectrometry (ICP-MS) and transmission electron microscopy (TEM) it was observed that AgNPs translocated from the blood to the main organs and the concentration of silver in tissues was significantly higher in rats treated with 20 nm AgNPs as compared with 200 nm AgNPs. The highest concentration of silver was found in the liver after 24 h. After 7 days, a high level of silver was observed in the lungs and spleen. The silver concentration in the kidneys and brain increased during the experiment and reached the highest concentration after 28 days. Moreover, the highest concentration of AgNPs was observed in the urine 1 day after the injection, maintained high for 14 days and then decreased. The fecal level of silver in rats was the highest within 2 days after AgNPs administration and then decreased.

Diminished amyloid-ß uptake by mouse microglia upon treatment with quantum dots, silver or cerium oxide nanoparticles: Nanoparticles and amyloid-ß uptake by microglia.

Alzheimer's disease (AD) is a chronic neurodegenerative disease leading to progressive dementia in elderly people. The disease is characterized, among others, by formation of amyloid-ß (Aß) polypeptide plaques in the brain. Although etiology of the disease is not fully understood, recent research suggest that nanomaterials may affect AD development. Here, we described the consequences of exposure of mouse BV-2 microglia to silver nanoparticles (AgNPs, 50 µg/mL), cerium oxide nanoparticles (CeO2NPs, 100 µg/mL), and cadmium telluride quantum dots (CdTeQDs, 3 or 10 µg/mL) in the context of its ability to clear Aß plaques. The brain microglial cells play an important role in removing Aß plaques from the brain. Cell viability and cycle progression were assessed by trypan blue test and propidium iodide binding, respectively. The uptake of Aß and NPs was measured by flow cytometry. Secretion of proinflammatory cytokines was measured with the use of cytometric bead array. Aß (0.1 µM) did not affect viability, whereas NPs decreased microglia growth by arresting the cells in G1 phase (CdTeQDs) or in S phase (AgNPs and CeO2NPs) of cell cycle. The uptake of Aß was significantly reduced in the presence of AgNPs and CeO2NPs. In addition, the least toxic CeO2NPs induced the release of proinflammatory cytokine, tumor necrosis factor α. In summary, each of the NPs tested affected either the microglia phagocytic activity (AgNPs and CeO2NPs) and/or its viability (AgNPs and CdTeQDs) that may favor the occurrence of AD and accelerate its development.

Comparison of the level(s) of DNA damage using Comet assay in bovine oocytes subjected to selected vitrification methods.

It was suggested that the cryodamage to oocytes' DNA has been responsible for the compromised developmental competence of cryopreserved oocytes. Vitrification of bovine oocytes affected not only cellular components, but also nuclear material. A significant rate of DNA fragmentation was found in bovine frozen or vitrified oocytes analysed by Comet assay regardless of cryopreservation method. Our method of vitrification using droplet system after gentle pre-equilibration treatment is one of the most effective cryopreservation methods employed for bovine oocytes so far, making it possible to develop 30% blastocyst stage embryos. In this study, the extent of DNA damage in bovine oocytes vitrified using three vitrification methods (droplet system, Open Pulled Straw and traditional vitrification in 0.25 ml insemination straws) was compared using Comet assay. Vitrification in droplet system and Open Pull Straws vitrification did not result in detectable cryoinjuries of DNA of bovine oocytes. On the contrary, DNA fragmentation was found in four of 26 oocytes vitrified in 0.25 ml straws (15.4%, p

Exposure of human neurons to silver nanoparticles induces similar pattern of ABC transporters gene expression as differentiation: Study on proliferating and post-mitotic LUHMES cells.

The Lund human mesencephalic (LUHMES) cell line originated from mesencephalon of 8-week human foetus is a renowned in vitro model of human dopaminergic neurons. After differentiation the cells exhibit dopaminergic and neuronal characteristics of biochemically and morphologically mature dopamine-like neurons. In this study we analysed expression of 42 genes from ABC transporter superfamily in both proliferating cells and differentiated neurons after treatment with silver nanoparticles. ABC transporter superfamily is especially known due to the involvement in multidrug resistance phenomenon, but also involvement in transport through blood-brain barrier. Our results indicate that in neurons silver nanoparticles mainly attenuate transporters responsible for maintaining asymmetry of cellular membrane and homeostasis of lipids and cholesterol. Our results revealed also that proliferating foetal brain cells are by far more susceptible to silver nanoparticles than differentiated neurons.

The effects of 1st and 2nd generation biodiesel exhaust exposure on hematological and biochemical blood indices of Fisher344 male rats - The FuelHealth project.

Diesel exhaust emissions (DEE), being one of the main causes of ambient air pollution, exert a detrimental effect on human health and increase morbidity and mortality related to cardiovascular and pulmonary diseases. Therefore, the objective of the present study was to investigate potential adverse effects of exhausts emissions from B7 fuel, the first-generation biofuel containing 7% of fatty acid methyl esters (FAME), and SHB20 fuel, the second-generation biofuel containing 20% FAME/hydrotreated vegetable oil (HVO), after a whole-body exposure with and without diesel particle filter (DPF). The experiment was performed on 95 male Fischer 344 rats, divided into 10 groups (8 experimental, 2 control). Animals were exposed to DEE (diluted with charcoal-filtered room air to 2.1-2.2% (v/v)) for 7 or 28 days (6 h/day, 5 days/week) in an inhalation chamber. DEE originated from Euro 5 engine with or without DPF treatment, run on B7 or SHB20 fuel. Animals in the control groups were exposed to clean air. Our results showed that the majority of haematological and biochemical parameters examined in blood were at a similar level in the exposed and control animals. However, exposure to DEE from the SHB20 fuel caused an increase in the number of red blood cells (RBC) and haemoglobin concentration. Moreover, 7 days exposure to DEE from SHB20 fuel induced genotoxic effects manifested by increased levels of DNA single-strand breaks in peripheral blood lymphocytes. Furthermore, inhalation of both types of DEE induced oxidative stress and caused imbalance of anti-oxidant defence enzymes. In conclusion, exposure to DEE from B7, which was associated with higher exposure to polycyclic aromatic hydrocarbons, resulted in decreased number of T and NK lymphocytes, while DEE from SHB20 induced a higher level of DNA single-strand breaks, oxidative stress and increased red blood cells parameters. Additionally, DPF technology generated increased number of smaller PM and made the DEE more reactive and more harmful, manifested as deregulation of redox balance.

Silver ions are responsible for memory impairment induced by oral administration of silver nanoparticles.

Increasing use of silver nanoparticles (AgNPs) results in increased human exposure. AgNPs are able to cross brain-blood barrier and are a risk factor for the brain. Thus, we hypothesized that AgNPs exposure might affect hippocampal dependent memory, which required cognitive coordination processes. To verify the assumption, in this study we evaluated the effects of orally administered bovine serum albumin (BSA)-coated AgNPs on spatial memory, which engage cognitive coordination processes for on-going stimuli segregation. Rats following 28 days of oral administration with 1 mg/kg (n = 10) or 30 mg/kg (n = 10) BSA-AgNPs or saline, a control groups (n = 10, n = 8), were tested with an active place avoidance task in the Carousel Maze test. The study revealed significant impairment of long- and short-term memory, irrespectively of dose of AgNPs, whereas non-cognitive activity was on a similar level. We found significantly higher content of silver in the hippocampus in comparison to the lateral cortex. No silver was found in the cerebellum and the frontal cortex. The nanoSIMS analysis reveal a weak signal of silver in the hippocampus of AgNPs treated animals that should be attributed to the presence of silver in ionic form rather than AgNPs. Our findings indicate that oral exposure to a low dose AgNPs induces detrimental effect on memory and cognitive coordination processes. The presence of silver ions rather than AgNPs in different brain regions, in particular the hippocampus, suggests crucial role of silver ions in AgNPs-induced impairment of the higher brain functions.

DNA damage and its repair in lymphocytes and thyroid nodule cells during radioiodine therapy in patients with hyperthyroidism.

Radioiodine treatment of hyperthyroid patients with autonomous thyroid nodule leads to cellular DNA damage not only in thyrocytes but also in peripheral blood lymphocytes. The purpose of this study was to evaluate DNA breakage and base damage in thyrocytes and lymphocytes in patients treated with 131-I. In all the patients thyroid scintiscan was performed using 131-I. Damage to DNA was estimated by comet assay. Samples were taken before radioiodine treatment, and 12 and 54 days afterwards. Our results indicate high diversity in the level of DNA damage among the individual patients. However, in all cases, after 54 days the level of DNA damage in lymphocytes was similar or even lower than that in the controls. In contrast, in hot nodule the DNA damage persisted until the 54th day after 131-I application. Differences in the type of DNA damage between thyrocytes and lymphocytes were also observed. In lymphocytes there was more base damage, whereas in thyrocytes single strand breaks prevailed. This may indicate different mechanisms of DNA damage induction and/or DNA repair.

Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis.

Differentiation-inducing agents, such as retinoids and short-chain fatty acids, have an inhibitory effect on tumor cell proliferation and tumor growth in preclinical studies. Clinical trials involving these compounds as single agents have been suboptimal in terms of clinical benefit. Our study evaluated the combination of phenylbutyrate (PB) and 13-cis retinoic acid (CRA) as a differentiation and antiangiogenesis strategy for prostate cancer. On the basis of previous evidence, common signal transduction pathways and possible modulation of retinoid receptors and retinoid response elements by PB could be responsible for such activities. We assessed the effect of the combination of PB and CRA on human and rodent prostate carcinoma cell lines. The combination of PB and CRA inhibited cell proliferation and increased apoptosis in vitro in an additive fashion as compared with single agents (P < 0.014). Prostate tumor cells treated with both PB and CRA revealed an increased expression of a subtype of retinoic acid receptor (retinoic acid receptor-beta), suggesting a molecular mechanism for the biological additive effect. The combination of PB and CRA also inhibited prostate tumor growth in vivo (up to 82-92%) as compared with single agents (P < 0.025). Histological examination of tumor xenografts revealed decreased in vivo tumor cell proliferation, an increased apoptosis rate, and a reduced microvessel density in the animals treated with combined drugs, suggesting an antiangiogenesis effect of this combination. Thus, endothelial cell treatment with both PB and CRA resulted in reduced in vitro cell proliferation. In vivo testing using the Matrigel angiogenesis assay showed an additive inhibitory effect in the animals treated with a combination of PB + CRA (P < 0.004 versus single agents). In summary, this study showed an additive inhibitory effect of combination of differentiation agents PB and CRA on prostate tumor growth through a direct effect on both tumor and endothelial cells.

Ionizing radiation and hydrogen peroxide induced oxidative DNA base damage in two L5178Y cell lines.

Seven oxidized DNA bases were quantified, by gas GC/MS-SIM, in chromatin from gamma-rays and H2O2 treated mouse lymphoma L5178Y (LY) cells, inversely cross-sensitive to these agents. In H2O2 treated cells (2 mM, 1 h, 37 degrees C) we found more damage in LY-R cells than in LY-S cells. On the contrary, in gamma-rays (400 Gy) treated cells we found more damaged DNA bases in LY-S cells. The yield of damaged bases in control cells was similar in both cell lines, with the exception of 8OHAde and FapyGua that were found at a much higher level in LY-S cells. The yields of damaged bases were related to cellular sensitivity to damaging agent; this observation points to a relationship between DNA base damage induction, antioxidant defense system in the intracellular milieu and cell sensitivity.

Further evidence that oxidative stress may be a risk factor responsible for the development of atherosclerosis.

There are numerous data suggesting that oxidative stress may be involved in the development of atherosclerosis. Therefore, in the present study we measured the amount of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), one of the typical biomarkers of oxidative stress, in DNA isolated from lymphocytes of the patients and in the control group. Levels of antioxidant vitamins (A, C, and E) and intracellular labile iron pool (LIP), which can influence oxidative stress, were also determined. Blood samples were obtained from a control group of 55 healthy persons and from 43 atherosclerotic patients. 8-OH-dG and the vitamin levels were measured by high-performance liquid chromatography. Labile iron pool in lymphocytes was analyzed by fluorescent assay. The levels of 8-OH-dG and LIP were significantly higher and vitamin C concentration was significantly lower in the patient group than in the control group. The rest of the analyzed parameters do not significantly differ between the groups. A lower concentration of vitamin C and higher levels of labile iron pool in a group of atherosclerotic patients when compared with the control group may lead to oxidative stress, which is manifested by a higher level of 8-OH-dG in blood lymphocytes. All these factors may create an environment that promotes the development of atherosclerosis.

Antioxidant defense system in differentially hydrogen peroxide sensitive L5178Y sublines.

Two sublines of L5178Y (LY) murine lymphoma, differing in sensitivity to hydrogen peroxide, served as a cellular model for examination of the antioxidant defense system. The contribution of catalase, glutathione peroxidase (G-Px) and glutathione were evaluated. Sensitivity to 3-amino-1,2,4-triazole (AMT), inhibitor of catalase, was higher in LY-R (hydrogen peroxide sensitive) than in LY-S (hydrogen peroxide resistant) cells. Accordingly, activity of catalase was twofold lower in LY-R than in LY-S cells. G-Px activity was about two times higher in LY-R than in LY-S cells. After induction with selenium it increased 15.6 times in LY-R cells and 50.3 times in LY-S cells. Reduced glutathione (GSH) content (and possibly other monobromobimane-reactive thiols) were determined fluorimetrically with monobromobimane and fluorescence found 54% higher in LY-S than in LY-R cells. Inhibition of catalase caused GSH decrease in LY-S cells; this decrease was abrogated by inducing G-Px by selenium treatment. On the contrary, in LY-R cells inhibition of catalase decreased GSH content only slightly and selenium treatment did not further change the GSH level. DNA damage (estimated by "comet" assay) was the same in hydrogen peroxide-treated cells in the presence or absence of AMT; however, after induction of G-Px by selenium, DNA damage was considerably lowered. This sparing effect of selenium was accompanied by decreased growth inhibition in selenium pretreated, hydrogen peroxide-treated cell cultures.

A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters.

Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of an attenuated mutant of diphtheria toxin A (tox176). Low expression levels of the DT-tox176 result in significant protein synthesis inhibition reflected by a decreased expression of the luciferase activity of a simultaneously transfected CMV luciferase construct. ID50 (dose of plasmid with 50% luciferase inhibition) was calculated for each promoter construct in different cell lines. Highest transactivational activity (ID50 <75 ng) was found for the CMV promoter in all cell lines, which is in agreement with the dual luciferase assay findings. Unlike the dual luciferase findings, however, the DT-tox176 assay showed protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells indicating "leakiness" of these promoter constructs. Low basal promoter activity in nonprostate cell lines was found for the minimal PSA promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better predict basal promoter activity compared to less sensitive dual luciferase assay.

Induction of DNA breakage in X-irradiated nucleoids selectively stripped of nuclear proteins in two mouse lymphoma cell lines differing in radiosensitivity.

The role of nuclear proteins in protection of DNA against ionizing radiation and their contribution to the radiation sensitivity was examined by an alkaline version of comet assay in two L5178Y (LY) mouse lymphoma cell lines differing in sensitivity to ionizing radiation. LY-S cells are twice more sensitive to ionizing radiation than LY-R cells (D0 values of survival curves are 0.5 Gy and 1 Gy, respectively). Sequential removal of nuclear proteins by extraction with NaCl of different concentrations increased the X-ray induced DNA damage in LY-R nucleoids. In contrast, in the radiation sensitive LY-S cell line, depletion of nuclear proteins practically did not affect DNA damage. Although there is no doubt that the main cause of LYS cells' sensitivity to ionizing radiation is a defect in the repair of double-strand breaks, our data support the concept that nuclear matrix organisation may contribute to the cellular susceptibility to DNA damaging agents.

Repair of gamma-ray-induced base damage in L5178Y sublines is damage type-dependent and unrelated to radiation sensitivity.

The L5178Y (LY) murine lymphoma sublines LY-R and LY-S are differentially sensitive to ionizing radiation. The high radiation sensitivity of LY-S cells is related to impaired rejoining of DNA double strand breaks. We found previously that the gamma-ray-induced base damage is higher in the more radiosensitive LY-S subline. Here, we examine the role of the repair of ionizing radiation induced base damage in relation to the radiosensitivity difference of these sublines. We used the GS/MS technique to estimate the repair rates of six types of base damage in gamma-irradiated LY cells. All modified DNA bases identified in the course of this study were typical for irradiated chromatin. The total amount of initial base damage was higher in the radiation sensitive LY-S subline than in the radiation resistant LY-R subline. The repair rates of 5-OHMeUra, 5-OHCyt, 8-OHAde were similar in both cell lines, the repair rates of FapyAde and 8-OHGua were higher in the radiosensitive LY-S cell line, whereas the repair of 5-OHUra was faster in its radioresistant counter, the LY-R. Altogether, the repair rates of the y-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the differential lethal or mutagenic effects of ionizing radiation in these sublines.

The response of L5178Y lymphoma sublines to oxidative stress: antioxidant defence, iron content and nuclear translocation of the p65 subunit of NF-kappaB.

We examined the response to hydrogen peroxide of two L5178Y (LY) sublines which are inversely cross-sensitive to hydrogen peroxide and X-rays: LY-R cells are radio-resistant and hydrogen peroxide-sensitive, whereas LY-S cells are radiosensitive and hydrogen peroxide-resistant. Higher initial DNA breaks and higher iron content (potentially active in the Fenton reaction) were found in the hydrogen peroxide sensitive LY-R cells than in the hydrogen peroxide resistant LY-S cells, whereas the antioxidant defence of LY-R cells was weaker. In particular, catalase activity is twofold higher in LY-S than in LY-R cells. The content of monobromobimane-reactive thiols is 54% higher in LY-S than in LY-R cells. In contrast, the activity of glutathione peroxidase (GPx) is about two times higher in LY-R than in LY-S cells; however, upon induction with selenium the activity increases 15.6-fold in LY-R cells and 50.3-fold in LY-S cells. Altogether, the sensitivity difference is related to the iron content, the amount of the initial DNA damage, as well as to the efficiency of the antioxidant defence system. Differential nuclear translocation of p65-NF-kappaB in LY sublines is due to the more efficient antioxidant defence in LY-S than in LY-R cells.

Effect of signal transduction inhibition in adapted lymphocytes: micronuclei frequency and DNA repair.

Irradiation of human lymphocytes (1 cGy X rays, 37 degrees C) or their treatment with 10 microM hydrogen peroxide (30 min at 37 degrees C) evoked a ca 30% decrease in the frequency of micronuclei upon subsequent X-irradiation (1.5 Gy). The response was reflected in a lower micronuclei frequency, but no change in DNA repair rate was observed as measured by the comet assay, directly after the challenge dose. Treatment of lymphocytes with staurosporine, an inhibitor of protein kinases, or with TMB-8, a calcium antagonist, carried out in parallel with the adaptive dose prevented the development of the adaptive response measured as micronuclei frequency. In lymphocytes that were staurosporine- or TMB-8-treated and irradiated under adaptive conditions showed that the rate of DNA repair was not changed. We conclude that treatment with agents that interfere with the transduction of the signal triggered by the low dose prevents the development of the adaptive response induced by X rays or hydrogen peroxide. Lower chromosome damage revealed by the cytokinesis block-micronuclei test in the adapted lymphocytes is unrelated to DNA repair rate as measured by comet assay.

Differential DNA double strand break fixation dependence on poly(ADP-ribosylation) in L5178Y and CHO cells.

PURPOSE: To investigate the role of poly(ADP-ribosylation) in DNA double-strand break repair and fixation in murine lymphoma L5178Y (LY) sublines, LY-R and LY-S, and a pair of Chinese hamster ovary lines: wild-type and mutant xrs6 cells, that have differences in repair competence and degree of radiosensitization with poly(ADP-ribosylation) inhibitors. MATERIALS AND METHODS: Cells (asynchronous, logarithmic phase) were pre-incubated with 2 mM aminobenzamide at 37 or 25 degrees C, X-irradiated with 10 Gy and allowed to repair DNA breaks for 15, 60 and 120 min at 37 or 25 degrees C. The remaining double-strand break were estimated by the neutral comet assay. RESULTS: At 37 degrees C, no effect of AB treatment on the repair kinetics was observed either in xrs6 or Chinese hamster ovary (wild-type) cells. In contrast, aminobenzamide decreased the repair of double-strand break in the LY-S line but not the LY-R line, in agreement with the previously observed radiosensitization of LY cells by poly(ADP-ribosylation) inhibition. However, double-strand break rejoining in the repair competent cell lines, Chinese hamster ovary and LY-R, also was affected by aminobenzamide when the post-irradiation incubation was carried out at 25 degrees C. Analysis of these results together with earlier data on LY-S cells have been interpreted in terms of Radford's model of radiation damage fixation. CONCLUSION: The reported results indicate that poly(ADP-ribosylation) can be an important modulator of the conversion of DNA damage to lethal events.

Interaction of some organic platinum (II) complexes with L5178Y-R and L5178Y-S cells.

The cytotoxicity and mutagenicity of three organic platinum(II) complexes 1-3 have been studied in two strains of murine lymphoma L5178Y cells. (1) [Pt(Amp)Cl] (S,N,N) (Amp, ampicillin); (2) [Pt(Met(O))Cl2] (S,N), (met(O), L-methionine sulfoxide); (3) [Pt(Met(O))(R-IDA)] (S,N) [N,N), (R-IDA, 2,4-N-(dimethylacetanilide)-iminodiacetic acid). It has been confirmed that the cytotoxic and mutagenic action of Pt-complexes depends on the structure of stable ligand and the number and structure of the leaving groups. The highest cytotoxicity and mutagenicity was found in cells treated with the dichloromethioninesulfoxideplatinum(II) complex.