Acrylamide in potato chips in Iran, health risk assessment and mitigation.

This study aimed to determine the acrylamide content in potato chips sold in Kermanshah, Iran and assess the potential health concerns associated with acrylamide exposure. HPLC-DAD was used to analyse 120 samples across 40 brands. The possible non-carcinogenic risk index for adults was below 1 for all 40 brands (100%), but for children it was only below 1 for 9 brands (22.5%) and above 1 for 31 brands (77.5%). Regarding the possible carcinogenic risk index, for adults only 1 out of 40 brands rated > 10-4, whereas for children all brands rated > 10-4. This shows that children's exposure to acrylamide through potato chips consumption in Kermanshah can be considered a risk on cancer and exposure of adults requires attention and monitoring. The best way to reduce acrylamide in potato chips and associated health risks is to improve the production process, especially temperature and time.

Euglena gracilis Extract Protects From Tobacco Smoke Carcinogen-Induced Lung Cancer by Altering Gut Microbiota Metabolome.

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.

Biogeochemical behaviour and toxicology of chromium in the soil-water-human nexus: A review.

Chromium (Cr) affects human health if it accumulates in organs to elevated concentrations. The toxicity risk of Cr in the ecosphere depends upon the dominant Cr species and their bioavailability in the lithosphere, hydrosphere, and biosphere. However, the soil-water-human nexus that controls the biogeochemical behaviour of Cr and its potential toxicity is not fully understood. This paper synthesizes information on different dimensions of Cr ecotoxicological hazards in the soil and water and their subsequent effects on human health. The various routes of environmental exposure of Cr to humans and other organisms are also discussed. Human exposure to Cr(VI) causes both carcinogenic and non-carcinogenic health effects via complicated reactions that include oxidative stress, chromosomal and DNA damage, and mutagenesis. Chromium(VI) inhalation can cause lung cancer; however, incidences of other types of cancer following Cr(VI) exposure are low but probable. The non-carcinogenic health consequences of Cr(VI) exposure are primarily respiratory and cutaneous. Research on the biogeochemical behaviour of Cr and its toxicological hazards on human and other biological routes is therefore urgently needed to develop a holistic approach to understanding the soil-water-human nexus that controls the toxicological hazards of Cr and its detoxification.

Risk assessment of short-term intake of pyrrolizidine alkaloids in food: derivation of an acute reference dose.

Pyrrolizidine alkaloids (PA) are phytochemicals that are known to act as human hepatotoxins and are also considered to be genotoxic carcinogens. Several plant-derived foods are frequently contaminated with PA, like teas and herbal infusions, spices and herbs or certain food supplements. With respect to the chronic toxicity of PA, the carcinogenic potential of PA is generally regarded as the critical toxicological effect. The risk assessment of the short-term toxicity of PA, however, is internationally less consistent. The characteristic pathological syndrome of acute PA toxicity is hepatic veno-occlusive disease. High PA exposure levels may lead to liver failure and even death as documented by several case reports. In the present report, we suggest a risk assessment approach for the derivation of an acute reference dose (ARfD) for PA of 1 µg/kg body weight per day based on a sub-acute animal toxicity study in rats after oral PA administration. The derived ARfD value is further supported by several case reports describing acute human poisoning following accidental PA intake. The here derived ARfD value may be used for PA risk assessment in cases where the short-term toxicity of PA is of interest in addition to the assessment of the long-term risks.

Assessment of Carcinogenic and Non-carcinogenic Risk of Exposure to Metals via Consumption of Coffee, Tea, and Herbal Tea in Iranians.

In the current study, we assessed health risk posed to Iranian consumers through exposure to metals via oral consumption of coffee, tea, and herbal tea of various trademarks collected from Iran market. Level of As, Cd, Cr, Cu, Fe, Hg, Ni, and Pb in 243 samples was quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES). The metal levels in coffee samples from different trademarks of a specific country had statistically similar levels of metals; however, metal levels differed significantly among brand names form different countries. Metal levels in tea samples differed significantly between domestic and imported products, while different trademarks of similar countries did not show significant variations in this respect. Metal level in herbal tea samples did not show significant variations among different trademarks. Nevertheless, it should be highlighted that mean concentrations of metals statistically differed among different herbal tea samples. Deterministic hazard quotients (HQs) were <1.0 for all non-carcinogenic metals and total hazard index (HI) values indicated no risk; however, probabilistic assessment calculated HI values >1. In both deterministic and probabilistic scenarios, carcinogenic metals As and Ni had an estimated incremental lifetime cancer risk (ILCR) of medium level while that of Pb indicated no cancer risk. Sensitivity analysis showed that the concentration of metals had the most significant effect on non-carcinogenic and carcinogenic risks.

Major chemical carcinogens and health exposure risks in some therapeutic herbal plants in Nigeria.

People of all ages and genders utilize herbal medicine to treat varieties of problems all around the world. The accumulation of Cd and Cr in therapeutic herbs (Adansonia digitata, Psidium guajava, and Carica papaya) can lead to a variety of health complications. These leaf extracts are used to treat varieties of ailments, including cancer, in the northern Nigerian states of Borno, Jigawa, and Kano. The researchers employed high-resolution continuous source atomic absorption spectrometry. The statistical parameters such as mean, range, minimum and maximum were computed along with one-way analysis of variance (ANOVA) to assess activity concentrations of Major Chemical Carcinogens (MCCs) in the herb extracts from the three states. The result demonstrated substantial statistical variation in the concentration of Chromium between groups with C. papaya (F = 190.683, p = 0.000), P. guajava (F = 5.698, p = 0.006), A. digitata (F = 243.154, p = 0.000). The post hoc test revealed that the C. papaya and A. digitata observed concentrations were statistically significant across the three states (p = 0.000). It was observed that there is no statistically significant difference between concentrations of the extracts between Kano and Borno states for P. guajava (p = 0.686). For Cd, the one-way ANOVA showed significant statistically variation in the concentration between groups with C. papaya (F = 77.393, p = 0.000), P. guajava (F = 4.496, p = 0.017), A. digitata (F = 69.042, p = 0.000). The post hoc test with multiple comparisons revealed that the activity concentration of all extracts was statistically significant across the three states (p<0.05). The target risk quotient (THQ) for Cd was more than unity in A. digitata and C. papaya, except for P. guajava from Borno State. The probable cancer risk was observed for consumption of plant extracts as a result of Cr and Cd.

Toxic Metals and Metalloids in Infant Formulas Marketed in Brazil, and Child Health Risks According to the Target Hazard Quotients and Target Cancer Risk.

Children are highly vulnerable to chemical exposure. Thus, metal and metalloid in infant formulas are a concern, although studies in this regard are still relatively scarce. Thus, the presence of aluminum, arsenic, cadmium, tin, mercury, lead, and uranium was investigated in infant formulas marketed in Brazil by inductively coupled plasma mass spectrometry, and the Target Hazard Quotients (THQ) and Target Cancer Risk (TCR) were calculated in to assess the potential risk of toxicity for children who consume these products continuously. Aluminum ranging from 0.432 ± 0.049 to 1.241 ± 0.113 mg·kg-1, arsenic from 0.012 ± 0.009 to 0.034 ± 0.006 mg·kg-1, and tin from 0.007 ± 0.003 to 0.095 ± 0.024 mg·kg-1 were the major elements, while cadmium and uranium were present at the lowest concentrations. According to the THQ, arsenic contents in infant formulas showed a THQ > 1, indicating potential health risk concerns for newborns or children. Minimal carcinogenic risks were observed for the elements considered carcinogenic. Metabolic and nutritional interactions are also discussed. This study indicates the need to improve infant formula surveillance concerning contamination by potentially toxic and carcinogenic elements.

Safest Roasting Times of Coffee To Reduce Carcinogenicity.

ABSTRACT: Roasting coffee results in not only the creation of carcinogens such as acrylamide, furan, and polycyclic aromatic hydrocarbons but also the elimination of carcinogens in raw coffee beans, such as endotoxins, preservatives, or pesticides, by burning off. However, it has not been determined whether the concentrations of these carcinogens are sufficient to make either light or dark roast coffee more carcinogenic in a living organism. An Ames test was conducted on light, medium, and dark roast coffee from three origins. We found that lighter roast coffee shows higher mutagenicity, which is reduced to the control level in dark roast coffee varieties, indicating that the roasting process is not increasing mutagenic potential but is beneficial to eliminating the existing carcinogens in raw coffee beans. This result suggests that dark roast coffee is safer and promotes further studies of the various carcinogens in raw coffee that have been burned off.

[Pediatric exposure to endocrine disruptors and carcinogenic, mutagenic or reprotoxic substances by pharmaceutical forms intended for the cutaneous route: Regulatory provisions in France, in Europe, and state of the art of scientific knowledge]. / Exposition pédiatrique aux perturbateurs endocriniens et substances cancérogènes, mutagènes ou reprotoxiques par des formes pharmaceutiques destinées à la voie cutanée : dispositions réglementaires en France, en Europe, et état de l'art des connaissances scientifiques.

OBJECTIVES: The objective is to conduct a review of pediatric exposure to substances whose endocrine disrupting (ED), carcinogenic, mutagenic, or reprotoxic (CMR) character has been confirmed or remains controversial, through their use in pharmaceutical forms intended for the cutaneous route, as well as regulatory measures diligent at the national and European levels. METHODS: A bibliographical search was carried out on the databases PubMed, Web of Science, Cochrane Library, supplemented by a search for recommendations from French and European authorities. References were selected following an assessment of their relevance to our topic. RESULTS: Seventy-one references were selected. Pediatric exposure to endocrine disruptors and CMR substances remains through products formulated for their use, but also through indirect exposure to products commonly used by adults. Exposure arises both from the choice of excipients (parabens, phenoxyethanol), packaging materials (bisphenols, phthalates) and the qualitative or quantitative nature of the active ingredients (iodine, boron, pyrethroids, organic sunscreens). CONCLUSION: The health professional must be able to develop a critical mind on such substances in order to inform and promote therapeutic adherence, guaranteeing the safety of the child's care.

Anticancer and antimutagenic activity of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. against skin cancer induced by DMBA: In vitro and in vivo models.

The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.

Ochratoxin a levels in fermented specialty coffees from Caparaó, Brazil: Is it a cause of concern for coffee drinkers?

Although postharvest coffee fruit fermentation can improve coffee flavour and quality, the mycotoxin ochratoxin A (OTA) can also be a result of microbiological activity, albeit in the later drying step of coffee processing. To evaluate the possible occurrence of OTA contamination in postharvest fruit fermentation, fourteen coffees that entailed two different postharvest fruit fermentation times were evaluated. These coffees originated in the surroundings of the village of Pedra Menina in the qualified Denomination of Origin and coffee producer region of Caparaó on the border between Minas Gerais and Espírito Santo states in Brazil. All coffees were classified according to the Specialty Coffee Association (SCA) protocol and 12 achieved specialty level. OTA was determined in all 14 coffees using immunoaffinity for sample clean-up and high-performance liquid chromatography with fluorescence detection for quantification. One sample presented an OTA concentration of 0.75 µg kg-1 and two samples showed OTA concentrations of 0.87 µg kg-1. The other samples had concentrations of OTA below the limit of quantification obtained in this work (0.64 µg kg-1). Thus, all samples showed OTA concentrations far below the most stringent maximum residue limit (MRL) of 5 µg kg-1 established for roasted coffees by European legislation. These low levels were similar to most of the previous results for Brazilian coffees listed and tabled in this work. This comparison showed that OTA contamination due to this kind of postharvest process - fruit fermentation - should not be a concern for producers and consumers of these fermented coffees.

Ellagitannins from jabuticaba (Myrciaria jaboticaba) seeds attenuated inflammation, oxidative stress, aberrant crypt foci, and modulated gut microbiota in rats with 1,2 dimethyl hydrazine-induced colon carcinogenesis.

Since dietary factors are thought to be responsible for high colon cancer risk, we investigated the chemopreventive effect of jabuticaba seed extract (LJE) by administering yogurt with or without LJE against 1,2 dimethyl hydrazine (DMH)-induced colon carcinogenesis in rats. Results showed that LJE contained a total phenolic content of 57.16 g/100 g of seed extract in which 7.67 and 10.09 g/100 g represented total flavonoids and ellagitannins, respectively. LJE protected DNA and human LDL against induced in vitro oxidation, which was associated with the ellagitannin content and with the free-radical scavenging and reducing capacities. LJE alone had a non-clastogenicity/aneugenicity property, but in combination with cisplatin, it enhanced the chromosome aberrations in cancer cells. In colon cancer-induced rats, yogurt with or without LJE caused a reduction in pro-inflammatory parameters, decreased the RNA expression of antiapoptotic cytokines and increased the expression of proapoptotic cytokines. Moreover, LJE attenuated colon cancer initiation and progression by decreasing aberrant crypt foci and LJE recovered the gut microbiome. Together, this evidence suggests that LJE provides chemopreventive protection against colon cancer development by reducing inflammation and increasing proapoptotic pathways.

Metformin alters therapeutic effects in the BALB/c tumor therapy model.

BACKGROUND: Despite considerable medical proceedings, cancer is still a leading cause of death. Major problems for tumor therapy are chemoresistance as well as toxic side effects. In recent years, the additional treatment with the antidiabetic drug metformin during chemotherapy showed promising results in some cases. The aim of this study was to develop an in vitro tumor therapy model in order to further investigate the potential of a combined chemotherapy with metformin. METHODS: Cytotoxic effects of a combined treatment on BALB/c fibroblasts were proven by the resazurin assay. Based on the BALB/c cell transformation assay, the BALB/c tumor therapy model was established successfully with four different and widely used chemotherapeutics from different categories. Namely, Doxorubicin as a type-II isomerase inhibitor, Docetaxel as a spindle toxin, Mitomycin C as an alkylating agent and 5-Fluorouracil as an antimetabolite. Moreover, glucose consumption in the medium supernatant was measured and protein expressions were determined by Western Blotting. RESULTS: Initial tests for the combined treatment with metformin indicated unexpected results as metformin could partly mitigate the cytotoxic effects of the chemotherapeutic agents. These results were further confirmed as metformin induced resistance to some of the drugs when applied simultaneously in the tumor therapy model. Mechanistically, an increased glucose consumption was observed in non-transformed cells as well as in the mixed population of malignant transformed cell foci and non-transformed monolayer cells, suggesting that metformin could also increase glucose consumption in transformed cells. CONCLUSION: In conclusion, this study suggests a cautious use of metformin during chemotherapy. Moreover, the BALB/c tumor therapy model offers a potent tool for further mechanistic studies of drug-drug interactions during cancer therapy.

Risk characterisation of constituents present in jamu to promote its safe use.

Safety in use of jamu consumption, as part of traditional medicine from Indonesia, is dependent on the complete and adequate assessment of potential hazards and risks of the botanicals and botanical constituents included. This includes especially hazards and risks related to the presence in jamu of active pharmaceutical ingredients (APIs) as well as of constituents that are genotoxic and carcinogenic. The present review presents an overview of the current state-of-the art on these hazards and risks based on case reports on adulteration, and the actual detection of genotoxic and carcinogenic ingredients of concern in jamu. Based on the overview thus obtained, it appears that drug-adulteration presents important hazards responsible for potential adverse effects, due to overdosing. The potential hazards of exposure to APIs mainly relate to the presence of constituents that may cause liver damage, renal impairment, kidney failure, steroid dependence or genotoxicity and carcinogenicity. For these APIs, a risk characterisation was performed based on comparison of health-based guidance values (HBGVs) and exposure, while for the genotoxic carcinogens the margin of exposure (MOE) approach was used. Results of this risk characterisation should be used by risk managers to impose specification for constituents of health concern to protect consumers. It is concluded that to manage the risks identified and further improve the safety in use of jamu, a collaboration between farmers, manufacturer/producers, academia, government, health professionals, and consumers is indicated.

Styrax camporum, a typical species of the Brazilian cerrado, attenuates DNA damage, preneoplastic lesions and oxidative stress in experimental rat colon carcinogenesis.

Styrax camporum Pohl, a typical species from the Brazilian cerrado, commonly known as "benjoeiro", is used to treat gastroduodenal diseases. In previous studies carried out by our research group, hydroalcoholic extract of S. camporum stems (SCHE) exhibited antigenotoxic and antiproliferative effects. For a comparative analysis of the chemopreventive effect of SCHE, the aim of this study was to investigate the influence of SCHE against carcinogen 1,2-dimethylhydrazine (DMH)-induced DNA damage and pre-neoplastic lesions in Wistar rat colon. Animals were treated orally with SCHE at 250, 500 or 1000 mg/kg body weight in conjunction with a subcutaneous injection of DMH. DNA damage was assessed using the comet assay while tpre-neoplastic lesions by aberrant crypt foci (ACF) assay. The following hepatic oxidative stress markers were determined including activities of catalase (CAT) and glutathione S-transferase (GST) as well as levels of reduced glutathione (GSH) and malondialdehyde (MDA). Treatment with SCHE was not genotoxic or carcinogenic at the highest dose tested (1000 mg/kg b.w.). The extract effectively inhibited DNA damage and pre-neoplastic lesions induced by DMH administration at all concentrations tested. Measurement of CAT, and GST activities and levels of GSH showed that SCHE did not reduce oxidative processes. In contrast, treatment with SCHE (1000 mg/kg b.w.) decreased liver MDA levels. Taken together, these findings suggested the chemopreventive effect attributed to SCHE in colon carcinogenesis, may be related to its capacity to inhibit DNA damage as well as an antioxidant action associated with its chemical constituents egonol and homoegonol.

Reduced hepatic global hydroxymethylation in mice treated with non-genotoxic carcinogens is transiently reversible with a methyl supplemented diet.

Non-genotoxic carcinogens (NGCs) are known to cause perturbations in DNA methylation, which can be an early event leading to changes in gene expression and the onset of carcinogenicity. Phenobarbital (PB) has been shown to alter liver DNA methylation and hydroxymethylation patterns in mice in a time dependent manner. The goals of this study were to assess if clofibrate (CFB), a well-studied rodent NGC, would produce epigenetic changes in mice similar to PB, and if a methyl donor supplementation (MDS) would modulate epigenetic and gene expression changes induced by phenobarbital. CByB6F1 mice were treated with 0.5% clofibrate or 0.14% phenobarbital for 7 and 28 days. A subgroup of PB treated and control mice were also fed MDS diet. Liquid Chromatography-Ionization Mass Spectrometry (LC-MS) was used to quantify global liver 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels. Gene expression analysis was conducted using Affymetrix microarrays. A decrease in liver 5hmC but not 5mC levels was observed upon treatment with both CFB and PB with varying time of onset. We observed moderate increases in 5hmC levels in PB-treated mice when exposed to MDS diet and lower expression levels of several phenobarbital induced genes involved in cell proliferation, growth, and invasion, suggesting an early modulating effect of methyl donor supplementation. Overall, epigenetic profiling can aid in identifying early mechanism-based biomarkers of non-genotoxic carcinogenicity and increases the quality of cancer risk assessment for candidate drugs. Global DNA methylation assessment by LC-MS is an informative first step toward understanding the risk of carcinogenicity.

Evaluation of the carcinogenicity of dichloromethane in rats, mice, hamsters and humans.

Dichloromethane (DCM) is a high production volume chemical (>1000 t/a) mainly used as an industrial solvent. Carcinogenicity studies in rats, mice and hamsters have demonstrated a malignant tumor inducing potential of DCM only in the mouse (lung and liver) at 1000-4000 ppm whereas human data do not support a conclusion of cancer risk. Based on this, DCM has been classified as a cat. 2 carcinogen. Dose-dependent toxicokinetics of DCM suggest that DCM is a threshold carcinogen in mice, initiating carcinogenicity via the low affinity/high capacity GSTT1 pathway; a biotransformation pathway that becomes relevant only at high exposure concentrations. Rats and hamsters have very low activities of this DCM-metabolizing GST and humans have even lower activities of this enzyme. Based on the induction of specific tumors selectively in the mouse, the dose- and species-specific toxicokinetics in this species, and the absence of a malignant tumor response by DCM in rats and hamsters having a closer relationship to DCM toxicokinetics in humans and thus being a more relevant animal model, the current classification of DCM as human carcinogen cat. 2 remains appropriate.

Polycyclic aromatic hydrocarbons in coffee samples: Enquiry into processes and analytical methods.

Polycyclic aromatic hydrocarbons (PAHs) are considered to be potentially genotoxic and carcinogenic in humans. These ubiquitous environmental pollutants may derive from the incomplete combustion and pyrolysis of organic matter. Coffee is an extensively consumed drink, and its PAHs contamination is not only ascribed to environmental pollution, but mainly to the roasting processes. Although no fixed limits have yet been set for residual PAHs in coffee, the present review intends to summarise and discuss the knowledge and recent advances in PAHs formation during roasting. Because coffee origin and brewing operations may affect PAHs content, we thoroughly analysed the literature on extraction and purification procedures, as well as the main analytical chromatographic methods for both coffee powders and brews. With regards to the safety of this appreciated commodity, the control on the entire production chain is desirable, because of coffee beverage could contribute to the daily human intake of PAHs.

Novel therapeutic regimens for urethane-induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin-D3.

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Follow up long term preliminary studies on carcinogenic and toxic effects of ochratoxin A in rats and the putative protection of phenylalanine.

Carcinogenic effects of ochratoxin A (OTA) on liver, kidneys, intestine, lung and eyes of Wistar rats exposed to 10 ppm or 5 ppm OTA in the diet and additionally supplemented or not with phenylalanine (PHE) were examined during 24-months experimental period. OTA was seen to provoke strong degenerative changes and slight pericapillary oedema in most internal organs, e.g. kidneys, liver, intestine, spleen and brain. Six of total nine neoplasms were identified as malignant and three as benign. Five of total six malignant neoplasms and two of total three benign neoplasms were seen in male rats. The pathological finding in rats after two weeks feeding with OTA-contaminated feed was dominated by degenerative changes in various internal organs, which were weaker in the group additionally supplemented with PHE. The protective effect of PHE was evident with respect to OTA-induced decrease of serum glucose and serum protein, but this protection was not singnificant with respect to serum enzymes activity. The number of neoplasms in PHE-supplemented group exposed to 10 ppm OTA was similar to that in the group exposed to twice lower feed levels of OTA alone, suggesting about a possible protective effect of PHE. The rats would not be able to serve as experimental model for humans with regard to OTA-induced tumorigenesis, because the target organ of OTA-toxicity in humans and pigs is mainly the kidney as opposed to the significant damages and carcinogenic effects seen in various organs in rats exposed to OTA.