Carcinogenic Metabolites Research Articles

An unexpected butadiene diolepoxide-mediated genotoxicity implies alternative mechanism for 1,3-butadiene carcinogenicity

1,3-Butadiene (BD) is abundant in combustion products such as cigarette smoke. While BD has been classified as a known human carcinogen, a long-standing question is the identity of the ultimate carcinogenic metabolite in humans. We hypothesize that 3,4-epoxybutane-1,2-diol (EBD) may play a critical role in human carcinogenesis due to its high bioavailability. We utilized a differential toxicity assay for BD metabolites and newly synthesized EBD analogs in a series of isogenic chicken cells lacking specific DNA repair proteins to address the mode of action of BD genotoxicity and infer a mode of action. Surprisingly, as with the diepoxide 1,2:3,4-diepoxybutane (DEB), the monoepoxide EBD showed remarkable toxicity to cells deficient in Fanconi anemia (FANC) genes. This observation suggests that EBD may be transformed into a bifunctional metabolite and forms interstrand cross-links. EBD and its analog with a hydroxy substituent at C1 were found to be highly toxic to FANCD2-deficient chicken and human cells. The Results suggest that EBD may be transformed to a bifunctional epoxy aldehyde, perhaps by alcohol dehydrogenase, to which the observed FANC sensitivity could be attributed. The implications of this study are very important in considering mechanisms by which EBD may cause leukemia and lymphoma in humans exposed to BD.

Survey of consumption pattern, exposure and risk assessment of aflatoxins in different animal livers in Iran

Aflatoxins are a group of toxic and carcinogenic metabolites produced by fungal species that are found in a variety of foods. Due to the high consumption of liver in Iran and especially in Kermanshah province, in this study consumption patterns of liver types (Sheep, Cow, and Chicken), the aflatoxin levels of liver types (B1 and G1) and hazard indexes including estimated daily intake (EDI) and margin of exposure (MOE) were investigated. Results showed that males had the highest liver consumption (52.3%) than females with a marked tendency towards consuming sheep liver (80.7%). The results of HPLC analysis indicated that aflatoxin G1 was detected in all types of the liver. Also, the mean concentration of aflatoxin in samples taken from autumn to winter in cows, sheep and poultry liver was 1.823, 0.7605 and 0.446 μg/kg. The results of EDI shows that cow liver was 2.33 ng/kgbw/day and above the threshold and the MOE level for all three liver types showed a high risk of cancer with the chicken liver incurring the highest risk with MOE = 78.2. Therefore, it is required to adopt an effective strategy regarding community education, attention to food safety and liver consumption in Kermanshah city.

Risk of dietary and breastmilk exposure to mycotoxins among lactating women and infants 2-4 months in northern India.

Mycotoxins are carcinogenic secondary metabolites of fungi that have been linked to infant growth faltering. In this study, we quantified co‐occurring mycotoxins in breast milk and food samples from Haryana, India, and characterized determinants of exposure. Deterministic risk assessment was conducted for mothers and infants. We examined levels of eight mycotoxins (Aflatoxin B1, B2, G1, G2, M1, M2; Ochratoxin A, B) in 100 breast milk samples (infants 2–4 months) using ultra‐high‐performance liquid chromatography tandem mass spectrometry. Aflatoxin B1 (AFB1), fumonisin B1 (FB1) and deoxynivalenol (DON) were detected in several food items (n = 298) using enzyme‐linked immunosorbent assays. We report novel data on the presence of mycotoxins in breast milk samples from India. Whereas breast milk concentrations (AFM1 median: 13.7; range: 3.9–1200 ng/L) remain low, AFM1 was detected above regulatory limits in 27% of animal milk samples. Additionally, 41% of infants were above provisional maximum tolerable daily intake (PMTDI) limits for AFM1 due to consumption of breast milk (mean: 3.04, range: 0.26–80.7 ng kg−1 bw day−1). Maternal consumption of breads (p < 0.05) was associated with breast milk AFM1 exposure. AFB1 (μg/kg) was detected in dried red chilies (15.7; 0–302.3), flour (3.13; 0–214.9), groundnuts (0; 0–249.1), maize (56.0; 0–836.7), pearl millet (1.85; 0–160.2), rice (0; 0–195.6), wheat (1.9; 0–196.0) and sorghum (0; 0–63.5). FB1 (mg/kg) was detected in maize (0; 0–61.4), pearl millet (0; 0–35.4) and sorghum (0.95; 0–33.2). DON was not detected in food samples. Mothers in our study exceeded PMTDI recommendations for AFB1 due to consumption of rice and flour (mean: 75.81; range: 35.2–318.2 ng kg−1 bw day−1). Our findings show the presence of Aflatoxin B1 and M1 at various levels of the food chain and in breast milk, with estimated intakes exceeding PMTDI recommendations. Aflatoxins are known carcinogens and have also been linked to stunting in children. Their presence across the food system and in breast milk is concerning, thus warranting further research to replicate and expand on our findings and to understand implications for maternal and child health.

In vitro Detoxification of Aflatoxin B1 by Calcium Bentonite Clay Supplementation in Aflatoxigenic Mould Contaminated Feeds for Nile Tilapia, Oreochromis niloticus (Linnaeus, 1758)

Aflatoxins are toxic, carcinogenic secondary metabolites mainly produced by Aspergillus flavus fungi that is often detected in food and agricultural commodities. Calcium bentonite clay has been used historically as an anti-caking agent and a feed binder and demonstrated the ability to bind aflatoxins. Feed samples were prepared for Nile tilapia to determineaflatoxin detoxification properties of calcium bentonite clay. 0.5%, 1%, 1.5% and 2% of this clay was incorporated into Aspergillus flavus contaminated feed and labeled as TF1, TF2, TF3, TF4, and TF5 respectively. The determination and quantification of aflatoxins produced by the fungus in the feed samples were carried out by HPTLC method. The RF values of all the feed samples were confirmed to be the presence of aflatoxin B1 and AFB2, G1 and G2 toxins were not found in any of the samples. Results from this study revealed that the calcium bentonite clay at 2% effectively reduced AFB1 toxin by its adsorption properties. Moreover, calcium bentonite clay improved water stability, water absorption rate with minimal disintegration and nutrients leaching of feed samples in water.

CYP1B1 as a therapeutic target in cardio-oncology.

Cardiovascular complications have been frequently reported in cancer patients and survivors, mainly because of various cardiotoxic cancer treatments. Despite the known cardiovascular toxic effects of these treatments, they are still clinically used because of their effectiveness as anti-cancer agents. In this review, we discuss the growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects. CYP1B1 is an extrahepatic enzyme that is expressed in cardiovascular tissues and overexpressed in different types of cancers. A growing body of evidence is demonstrating a detrimental role of CYP1B1 in both cardiovascular diseases and cancer, via perturbed metabolism of endogenous compounds, production of carcinogenic metabolites, DNA adduct formation, and generation of reactive oxygen species (ROS). Several chemotherapeutic agents have been shown to induce CYP1B1 in cardiovascular and cancer cells, possibly via activating the Aryl hydrocarbon Receptor (AhR), ROS generation, and inflammatory cytokines. Induction of CYP1B1 is detrimental in many ways. First, it can induce or exacerbate cancer treatment-induced cardiovascular complications. Second, it may lead to significant chemo/radio-resistance, undermining both the safety and effectiveness of cancer treatments. Therefore, numerous preclinical studies demonstrate that inhibition of CYP1B1 protects against chemotherapy-induced cardiotoxicity and prevents chemo- and radio-resistance. Most of these studies have utilized phytochemicals to inhibit CYP1B1. Since phytochemicals have multiple targets, future studies are needed to discern the specific contribution of CYP1B1 to the cardioprotective and chemo/radio-sensitizing effects of these phytochemicals.

Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence.

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.

Validation of self-reported tobacco use with urinary NNAL among LCS-eligible population from the 2007-2014 National Health and Nutrition Examination Survey (NHANES)

Background As a major metabolite of tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) has been used as a biomarker for tobacco smoking exposure. Among current or former smokers, accurate self-reported smoking status is critical for determining the eligibility for lung cancer screening (LCS). This study used NNAL to verify self-reported smoking status among LCS-eligible population from a nationally representative sample in the National Health and Nutrition Examination Survey (NHANES). Methods We utilized NHANES data from 2007-2014 that included both urine total NNAL and self-reported smoking behavior to select the LCS-eligible population. We applied four cutpoints of NNAL (10pg/ml, 20pg/ml, 30pg/ml, 40pg/ml) as the gold standard to assess the performance of self-reported smoking status. To determine the validity and reliability of self-reported smoking status, we calculated the sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), accuracy, and reliability (Kappa). Results We found approximately 3.7% (n=985, equivalent to 8.5 million weighted population) of adults eligible for LCS according to the United States Preventive Services Task Force guideline. Validity and reliability of self-reported smoking status increased with increasing cutpoints of NNAL. Against NNAL-based smoking status with a cutpoint of 40pg/ml, self-reported smoking status showed the highest Se (88.8%), lowest Sp (99.4%); the corresponding PPV and NPV, respectively, was 99.5% and 85.5%; the accuracy was 93.0% and kappa was 0.86. The self-reported smoking status tended to be more valid and reliable among females than males across all NNAL cutpoints evaluated. Using the established 40pg/ml cutpoint as the gold standard, we found the accuracy was lowest among the non-Hispanic black (90.1%) and highest among the other race/ethnicity groups (93.9%). Conclusion Utilizing urine NNAL as the biochemical verification reference, we found that self-reported smoking status among people who are at risk of lung cancer is reasonably reliable.

The explosive trinitrotoluene (TNT) induces gene expression of carbonyl reductase in the blue mussel (Mytilus spp.): a new promising biomarker for sea dumped war relicts?

Millions of tons of all kind of munitions, including mines, bombs and torpedoes have been dumped after World War II in the marine environment and do now pose a new threat to the seas worldwide. Beside the acute risk of unwanted detonation, there is a chronic risk of contamination, because the metal vessels corrode and the toxic and carcinogenic explosives (trinitrotoluene (TNT) and metabolites) leak into the environment. While the mechanism of toxicity and carcinogenicity of TNT and its derivatives occurs through its capability of inducing oxidative stress in the target biota, we had the idea if TNT can induce the gene expression of carbonyl reductase in blue mussels. Carbonyl reductases are members of the short-chain dehydrogenase/reductase (SDR) superfamily. They metabolize xenobiotics bearing carbonyl functions, but also endogenous signal molecules such as steroid hormones, prostaglandins, biogenic amines, as well as sugar and lipid peroxidation derived reactive carbonyls, the latter providing a defence mechanism against oxidative stress and reactive oxygen species (ROS). Here, we identified and cloned the gene coding for carbonyl reductase from the blue mussel Mytilus spp. by a bioinformatics approach. In both laboratory and field studies, we could show that TNT induces a strong and concentration-dependent induction of gene expression of carbonyl reductase in the blue mussel. Carbonyl reductase may thus serve as a biomarker for TNT exposure on a molecular level which is useful to detect TNT contaminations in the environment and to perform a risk assessment both for the ecosphere and the human seafood consumer.

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

In Memoriam: Mortimer L. Mendelsohn: (1 December, 1925-8 January, 2020).

The interplay of the oral microbiome and alcohol consumption in oral squamous cell carcinomas.

Oral cancer (OC) is among the top twenty occurring cancers in the world, with a mortality rate of 50%. A shift to a functionally inflammatory or a 'disease state' oral microbiome composition has been observed amongst patients with premalignant disorders and OC, with evidence suggesting alcohol could be exacerbating the inflammatory influence of the oral microorganisms. Alcohol dehydrogenase (ADH, EC 1.1.1.1) converts alcohol into a known carcinogenic metabolite, acetaldehyde and while ADH levels in oral mucosa are low, several oral commensal species possess ADH and could produce genotoxic levels of acetaldehyde. With a direct association between oral microbiome status, alcohol and poor oral health status combining to induce chronic inflammation with increased acetaldehyde levels - this leads to a tumour promoting environment. This new disease state increases the production of reactive oxygen species (ROS), while impairing anti-oxidant systems thus activating the redox signalling required for the promotion and survival of tumours. This review aims to highlight the evidence linking these processes in the progression of oral cancer.

MAPK pathway-related tyrosine phosphatases regulate development, secondary metabolism and pathogenicity in fungus Aspergillus flavus.

Mitogen-activated protein kinase (MAPK) cascades are highly conserved in eukaryotic cells and are known to play crucial roles in the regulation of various cellular processes. However, compared with kinase-mediated phosphorylation, dephosphorylation catalysed by phosphatases has not been well characterized in filamentous fungi. In this study, we identified five MAPK pathway-related phosphatases (Msg5, Yvh1, Ptp1, Ptp2 and Oca2) and characterized their functions in Aspergillus flavus, which produces aflatoxin B1 (AFB1 ), one of the most toxic and carcinogenic secondary metabolites. These five phosphatases were identified as negative regulators of MAPK (Slt2, Fus3 and Hog1) pathways. Deletion of Msg5 and Yvh1 resulted in significant defects in conidiation, sclerotia formation, aflatoxin production and crop infection. Additionally, double knockout mutants (ΔMsg5/ΔPtp1, ΔMsg5/ΔPtp2 and ΔMsg5/ΔOca2) displayed similar defects to those observed in the ΔMsg5 single mutant, indicating that Msg5 plays a major role in the regulation of development and pathogenicity in A. flavus. Importantly, we found that the active site at C439 is essential for the function of the Msg5 phosphatase. Furthermore, the MAP kinase Fus3 was found to be involved in the regulation of development, aflatoxin biosynthesis and pathogenicity, and its conserved phosphorylation residues (Thr and Tyr) were critical for the full range of its functions in A. flavus. Overall, our results reveal that MAPK related tyrosine phosphatases play important roles in the regulation of development, secondary metabolism and pathogenicity in A. flavus, and could be developed as potential targets for preventing damage caused by this fungal pathogen.

Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition.

Although what unifies the carcinogenic microorganisms has not been determined by multiple studies, the role of bacteria in the development of neoplasms has not been properly elucidated. In this review, we discuss links between the bacterial species and cancer, with focus on immune responses for the stimulation of tumor cells such as induction of inflammation. Finally, we will describe the potential therapeutic strategies of bacteria on target tumors to improve treatment while mitigating adverse reactions. Cancer is a series of genetic changes that transform normal cells into tumor cells. These changes come from several reasons, including smoking, drinking alcohol, sunlight, exposure to chemical or physical factors, and finally chronic infection with microorganisms, including bacteria. In fact, bacterial infections are not carcinogenic, but recently it was discovered that the association between bacteria and cancer is through two mechanisms, the first stimulating chronic inflammation and the second producing carcinogenic metabolites. While bacteria are carcinogenic agents also, they have a dual role eliminating and removing tumor cells. However, the traditional cancer treatments that include chemotherapy, radiotherapy, surgery, and immunotherapy increase the chances of survival, and there are many side effects of these therapies, including the high toxicity of tissues and normal cells, could not penetrate the tumor cells, and resistance of these therapies by tumor cells. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer. Also, bacteria can be used as vectors for drug, gene, or therapy, and this is a great step to treat cancer. Thus, we review the mechanisms underlying the interaction of the microbiota residents with cancer. Cancer-associated bacteria differ from those in healthy human and are linked with gene-expression profile. We also discuss how live bacteria interact with tumor microenvironments to induce tumor regression through colonization and spread. Finally, we provide past and ongoing clinical trials that include bacteria targeting tumors.

Abstract 4668: Human CYP1B1 prevents TRAIL-DR4-mediated cancer cell apoptosis through downregulation of miR-375

Abstract Human cytochrome P450 1B1 (CYP1B1) is an important enzyme that catalyzes metabolism of 17β-estradiol (E2) to catechol estrogens, including carcinogenic metabolite 4-hydroxyestradiol (4-OHE2). CYP1B1 may play a crucial role in estrogen-mediated carcinogenesis since CYP1B1 shows tumor-specific expression pattern in various hormone-responsive tissues. However, the detailed mechanism of CYP1B1-dependent carcinogenesis remains still unclear. Here, we investigated the association between TRAIL, DR4, and CYP1B1 expression in human tumor cells, including MCF-7, MDA-MB-231, and HeLa cells. CYP1B1 can inhibit the expression and release of TRAIL simultaneously with the expression of the death receptor DR4/5, known as TRAIL receptors, to prevent apoptosis. Furthermore, we found that CYP1B1 represses the transcription of DR4 by inducing DNA methylation in the promoter region of DR4. In addition, we revealed that CYP1B1 regulates TRAIL and DR4 through activation of Sp1 transcription factor. CYP1B1 and its enzymatic product, 4-OHE2, promote Sp1 expression levels in both mRNA and protein levels. Interestingly, CYP1B1 elevated Sp1 through downregulation of miR-375, which is a candidate tumor suppressive microRNA and transcriptional inhibitor of Sp1. Taken together, our data suggest that CYP1B1 inhibits TRAIL-DR4-mediated cancer cell apoptosis through induction of Sp1 through repression of miR-375, which promotes cancer cell survival. Citation Format: Yeo-Jung Kwon, Dong-Jin Ye, Huoung-Seok Baek, Sangyun Shin, Tae-Uk Kwon, Eunah Cho, Hong-Gyu Ahn, Youngjin Chun. Human CYP1B1 prevents TRAIL-DR4-mediated cancer cell apoptosis through downregulation of miR-375 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4668.

Detection of Aflatoxins from Malt Barley Under Storage Conditions in Central Ethiopia

Aflatoxins are non avoidable highly poisonous and carcinogenic auxiliary metabolite produced by some molds belonging to Aspergillus genera on range of agricultural products including malt barley. This study was conducted with the aim to examine total aflatoxin (AFT) concentration in malt barley samples. A total of eighty seven malt barley samples collected from farmers' stores and seed enterprises' of Amhara and Oromia regions were employed for aflatoxin analysis through an ELISA test. Of these, 30 (34.48%) were positive whereas the remaining 57 (54.03%) were negative. The total aflatoxin levels in the positive samples layover in a range between 0.0005μgkg -1 and 0.04μgkg -1 .The existing results undoubtedly revealed insignificant contamination of malt barley samples in Ethiopia, suggesting that concentrations were low enough and ensure compliance with the Food and Agricultural Organization of the United Nations (FAO) 20 ugkg -1 , World Health Organization (WHO) 15 μgkg -1 and European Union (EU) 4-15ugkg -1 admitted levels depending on the raw material use of cereals. Fortunately, the result of this study may not lead to infer the urgent need to apply control measures against aflatoxigenic fungi and associated aflatoxins that could result adverse effects. The major factors for less contamination of malt barley by aflatoxin were expected to be pre- and post-harvest environmental factors, mechanized harvesting and proper management practices like drying before storage. Although the present status of aflatoxins is remarkably at lower concentrations, regular and accurate cereal quality testing is critical to reduce the risk of severe health problems as well as international trade repercussions. Keywords: Adverse effect, Auxiliary metabolite, Contamination, ELISA, Molds. DOI: 10.7176/JBAH/10-15-01 Publication date: August 31 st 2020

Health effects of electronic cigarette (e‑cigarette) use on organ systems and its implications for public health.

BackgroundThere has been growing concern over the use of electronic cigarettes (e-cigarettes) in recent years. Although advocated as an aid to smoking cessation, there is increasing evidence of harm not just to the respiratory system, but to all other organs in the body. To give a clearer picture on how e‑cigarettes can affect our health, we gathered an overview of the literature on the various health effects of e‑cigarettes and categorized them into how they specifically affect organ systems.E‑cigarette exposure has produced a range of stress and inflammatory reactions in the pulmonary system, including shortness of breath, coughing, wheezing, bronchial and pulmonary irritations, and impaired pulmonary function. In the oral and gastrointestinal system, gingival inflammation, sore throat, nausea, vomiting, and diarrhea have been reported. Increased tachycardia and blood pressure were reported reactions in the cardiovascular system. In the neurological system headaches, irritability, anxiety, dependence and insomnia were observed. Other effects included ocular irritation, contact dermatitis, acute renal insufficiency, toxicity and potential carcinogenicity. Nevertheless, studies have found improvements in time-based memory and nicotine withdrawal associated with the cessation of conventional cigarette smoking and switching to e‑cigarette use. Also, toxic and carcinogenic metabolites were reportedly lower in e‑cigarette smokers than in conventional cigarette smokers.ConclusionA growing number of studies are showing the adverse effects caused by e‑cigarettes on all human organ systems. Further research on the chemical components, the diverse flavors, and the long-term effects on active and passive users are needed to clarify the implications of e‑cigarette use on individual and public health.

Inhibitory effect of Capsicum chinense and Piper nigrum fruits, capsaicin and piperine on aflatoxins production in Aspergillus parasiticus by downregulating the expression of aflD, aflM, aflR, and aflS genes of aflatoxins biosynthetic pathway

Aflatoxins produced by Aspergillus parasiticus are toxic and carcinogenic metabolites. The biosynthesis of this mycotoxins is a complex process and involves at least 30 genes clustered within an approximately 82 kB gene cluster. In the present study, the effect of Capsicum chinense and Piper nigrum fruits on Aspergillus parasiticus growth and aflatoxin production were studied in relation to the expression of aflD, aflM, aflR, and aflS four; key genes of aflatoxins biosynthesis pathway. GC-EIMS analysis identified capsaicin (66,107 µg g−1) and piperine (1,138 µg g−1) as the most abundant compounds in C. chinense and P. nigrum fruits, respectively. The antifungal and anti-aflatoxigenic assays showed that C. chinense, P. nigrum, capsaicin, and piperine inhibited A. parasiticus growth and aflatoxins production in a dose-dependent manner. The piperine at 300 µg mL−1 produced higher radial growth inhibition (89%) and aflatoxin production inhibition (69%). The expression of aflatoxin biosynthetic genes was evaluated by quantitative real-time PCR (qRT-PCR) and revealed that aflatoxin inhibition occurring via downregulating the aflS and aflR, and subsequently aflD and aflM genes. These results will improve our understanding of the mechanism of aflatoxin regulation by C. chinense, P. nigrum, capsaicin, and piperine, and provides a reference for further study.

In vitro and in vivo capacity of yeast-based products to bind to aflatoxins B1 and M1 in media and foodstuffs: A systematic review and meta-analysis

The aflatoxins are hepatotoxic and carcinogenic metabolites produced by Aspergillus species during growth on crop products. In this regard, a systematic review to collect the quantitative data regarding the in vitro capacity of yeasts-based products to bind to aflatoxin B1 (AFB1) and/or aflatoxin M1 (AFM1) was performed. After screening, 31 articles which met the inclusion criteria was included and then the pooled decontamination of aflatoxins in the defined subgroups (the type of foods, pH, contact time, temperature, yeast species, and aflatoxin type) was calculated by the random effect model (REM). The overall binding capacity (BC) of aflatoxins by yeast was 52.05% (95%CI: 49.01–55.10), while the lowest and highest aflatoxins’ BC were associated with Yeast Extract Peptone (2.79%) and ruminal fluid + artificial saliva (96.21%), respectively. Regarding the contact time, temperature, pH and type of aflatoxins subgroups, the binding percentages varied from 50.83% (>300 min) to 52.66% (1–300 min), 50.71% (0–40 °C) to 88.39% (>40 °C), 43.03% (pH: 3.1–6) to 44.56% (pH: 1–3) and 59.35% (pH > 6), and 48.47% (AFB1) to 69.03% AFM1, respectively. The lowest and highest aflatoxins’ BC was related to C. fabianii (18.45%) and Z. rouxii (86.40%), respectively. The results of this study showed that variables such as temperature, yeast, pH and aflatoxin type can be considered as the effective factors in aflatoxin decontamination.

1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP)-Cysteine Conjugates: Metabolic Formation and Binding to Cellular DNA.

1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that the reaction of 1-CHO-DHP with cysteine generated four identified products. By mass and 1H NMR spectral analyses, these products are cysteinyl-[2'-S-7]-1-CHO-DHP (P2), cysteinyl-[3'-N-7]-1-CHO-DHP (P3), 7-keto-DHP (P4), and 1-cysteinylimino-DHP (P5). These four compounds were also formed from the incubation of 1-CHO-DHP in HepG2 cells. Compounds P3 and P5 were interconvertible in acetonitrile and water. Incubation of P2 in HepG2 cells generated the four DHP-dG and -dA adducts that we propose to be potential common biomarkers of pyrrolizidine alkaloids exposure and pyrrolizidine alkaloids-induced liver tumor initiation. These four DHP-DNA adducts were also formed from the incubation of a mixture of P3 and P5 in HepG2 cells but not from the incubation with 7-keto-DHP. From the reaction of 1-CHO-DHP with glutathione, only trace amounts of the glutathione-1-CHO-DHP adduct were detected, with the structure unable to be characterized.

Prevalence of some Gram-Negative Bacteria and Adenovirus in Breast Cancer Patients in Kirkuk City

Background: Breast cancer is one of the most prevalent types of malignant tumors in the world. Bacteria have been linked with cancer through two mechanisms, the first, stimulating chronic inflammation, and the second, production of carcinogenic bacterial metabolites. The most common types of adenovirus in cancer patients are serotypes 7 and 11 of type B, and serotypes 1, 2, and 5 are of type C. Methods: In this study, 98 blood and 50 urine, samples were collected from women with breast cancer at the Center for Oncology and Hematology in Kirkuk city in addition to 30 blood and 20 urine samples collected from healthy persons as control. Pathogenic gram-negative bacteria were isolated, identified in addition to checking their susceptibility to antibiotics. Antibodies (IgM, IgG) of adenovirus type-7 were involved in this study by the ELISA technique. Results: In this study, 22 gram-negative bacterial species were isolated from patients with breast cancer, including (31.81% Klebsiella pneumoniae, 45.45% E. coli, 18.18% Proteus mirabilis and 4.54% Acinetobacter baumannii). Gram-negative bacteria showed high resistance to antibiotics (approximately absolute resistance) amoxicillin/clavulanic acid, ampicillin, ceftazidime, amoxicillin, cephalothin, vancomycin. Adenovirus type-7 antibodies were detected by using the ELISA technique (3.84% IgM and 91.02% IgG). Viral and bacterial co-infection were also included in this study caused by the involvement of Escherichia coli + ADV-7, P. mirabilis + ADV-7, and K. pneumoniae + ADV-7.

SPR nanosensor based on molecularly imprinted polymer film with gold nanoparticles for sensitive detection of aflatoxin B1

Aflatoxins which are highly toxic, immunosuppressive and carcinogenic secondary metabolites produced naturally by Aspergillus flavus fungal species have a harm effect on human and animal health. Label free and rapid sensing of aflatoxin B1 (AFB1) has drawn the increased interest of highly sensitive and selective research. A highly sensitive and selective plasmonic sensing method was developed for the detection of AFB1 based on enhance-surface plasmon resonance nanosensor. Firstly, AFB1 and N-methacryloyl-l-phenylalanine were pre-complexed as a template molecule and functional monomer. Molecularly imprinted polymers with gold nanoparticles were coated onto surface plasmon resonance (SPR) gold chip surface. The AFB1 imprinted nanosensor shown a wide linear range, between 0.0001 ng mL−1 and 10.0 ng mL−1, and the limit of detection is 1.04 pg mL−1. Compared to the non-imprinted nanosensor, the imprinting factor was found to be 5.91. Also, detection studies of AFB1 were performed using various food samples. Finally, SPR nanosensors were performed selectivity, reusability and storage stability analysis.