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CHEMICAL CARCINOGENESIS

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https://www.readbyqxmd.com/read/28441709/association-of-cyp3a5-3-and-cyp1a1-2c-polymorphism-with-development-of-acute-myeloid-leukemia-in-egyptian-patients
#1
Nahed Abd El Wahab, Nevine F Shafik, Roxan E Shafik, Sherin A Taha, Hanan E Shafik, Amira D Darwish
Aim: Cytochrome P450 (CYP) enzyme catalyzes the phase I metabolism reaction which metabolize endogenous and exogenous DNA-reactive chemical compounds and xenobiotics which could induce genotoxicity and increase the risk for leukemia. We aimed to detect frequency of CYP3A5*3 and CYP1A1*2C polymorphisms in Egyptian acute myeloid leukemia (AML) patients and to determine role of allele’s variants as a risk factor for developing leukemia. Patients and Methods: A case-control study was conducted on seventy acute myeloid leukemia patients and thirty control subjects...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28436299/mgmt-gene-variants-temozolomide-myelotoxicity-and-glioma-risk-a-concise-literature-survey-including-an-illustrative-case
#2
Meric A Altinoz, Ilhan Elmaci, Fatih Han Bolukbasi, Cumhur Gokhan Ekmekci, Guven Yenmis, Ramazan Sari, Aydin Sav
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment...
April 23, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28428278/oncogenic-role-of-snd1-in-development-and-progression-of-hepatocellular-carcinoma
#3
Nidhi Jariwala, Devaraja Rajasekaran, Rachel G Mendoza, Xue-Ning Shen, Ayesha Siddiq, Maaged Akiel, Chadia L Robertson, Mark A Subler, Jolene Windle, Paul B Fisher, Arun J Sanyal, Devanand Sarkar
SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-kappaB signaling pathways in promoting TIC formation in Alb/SND1 mice...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28422719/fbxw7-haploinsufficiency-loses-its-protection-against-dna-damage-and-accelerates-mnu-induced-gastric-carcinogenesis
#4
Yannan Jiang, Xinming Qi, Xinyu Liu, Jun Zhang, Jun Ji, Zhenggang Zhu, Jin Ren, Yingyan Yu
Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor suppressor via inducing apoptosis and growth arrest in various kinds of tumors. To clarify the initiating role in gastric carcinogenesis as well as the histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421967/lung-tumor-induction-by-26-week-dermal-application-of-1-2-dichloroethane-in-cb6f1-tg-rash2-mice
#5
Mayuko Suguro, Takamasa Numano, Mayumi Kawabe, Yuko Doi, Norio Imai, Yukinori Mera, Seiko Tamano
Short-term alternatives to traditional 2-year carcinogenic studies in rodents are being actively pursued. Recently, a 26-week short-term carcinogenicity study using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the evaluation of chemical carcinogenesis. However, an acceptable short-term carcinogenic study model for dermally applied products is still lacking. To investigate the suitability of using the rasH2 mouse to test carcinogenic potential, 1,2-dichloroethane (1,2-DCE) was dermally applied to rasH2 mice: 1,2-DCE is a known carcinogen that causes lung bronchiolo-alveolar adenomas and adenocarcinomas when administered topically, orally, or by inhalation exposure; 1,2-DCE at a dose level of 126 mg/mouse in 200 μl acetone or acetone alone (vehicle control) was applied to the dorsal skin of 10 mice of each sex 3 times a week for 26 weeks...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28416454/e1a-is-an-exogenous-in%C3%A2-vivo-tumour-suppressor
#6
F J Cimas, J L Callejas-Valera, D C García-Olmo, J Hernández-Losa, P Melgar-Rojas, M J Ruiz-Hidalgo, R Pascual-Serra, M Ortega-Muelas, O Roche, P Marcos, E Garcia-Gil, D M Fernandez-Aroca, S Ramón Y Cajal, J S Gutkind, R Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent)...
April 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28411036/prolonged-particulate-chromate-exposure-does-not-inhibit-homologous-recombination-repair-in-north-atlantic-right-whale-eubalaena-glacialis-lung-cells
#7
Cynthia L Browning, Catherine F Wise, John Pierce Wise
Chromosome instability is a common feature of cancers that forms due to the misrepair of DNA double strand breaks. Homologous recombination (HR) repair is a high fidelity DNA repair pathway that utilizes a homologous DNA sequence to accurately repair such damage and protect the genome. Prolonged exposure (>72h) to the human lung carcinogen, particulate hexavalent chromium (Cr(VI)), inhibits HR repair, resulting in increased chromosome instability in human cells. Comparative studies have shown acute Cr(VI) exposure induces less chromosome damage in whale cells than human cells, suggesting investigating the effect of this carcinogen in other species may inform efforts to prevent Cr(VI)-induced chromosome instability...
April 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28405246/modulation-of-benzo-a-pyrene-dna-adduct-formation-by-cyp1-inducer-and-inhibitor
#8
REVIEW
Kazuhiro Shiizaki, Masanobu Kawanishi, Takashi Yagi
Benzo[a]pyrene (BaP) is a well-studied pro-carcinogen that is metabolically activated by cytochrome P450 enzymes. Cytochrome P4501A1 (CYP1A1) has been considered to play a central role in the activation step, which is essential for the formation of DNA adducts. This enzyme is strongly induced by many different chemical agents, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which binds to the aryl hydrocarbon receptor (AhR). Therefore, AhR activators are suspected to have the potential to aggravate the toxicity of BaP through the induction of CYP1A1...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28393135/identification-of-4-3-pyridyl-4-oxobutyl-2-deoxycytidine-adducts-formed-in-the-reaction-of-dna-with-4-acetoxymethylnitrosamino-1-3-pyridyl-1-butanone-a-chemically-activated-form-of-tobacco-specific-carcinogens
#9
Anna K Michel, Adam T Zarth, Pramod Upadhyaya, Stephen S Hecht
Metabolic activation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) and N'-nitrosonornicotine (NNN, 2) results in the formation of 4-(3-pyridyl)-4-oxobutyl (POB)-DNA adducts, several of which have been previously identified both in vitro and in tissues of laboratory animals treated with NNK or NNN. However, 2'-deoxycytidine adducts formed in this process have been incompletely examined in previous studies. Therefore, in this study we prepared characterized standards for the identification of previously unknown 2'-deoxycytidine and 2'-deoxyuridine adducts that could be produced in these reactions...
March 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28366709/architecture-in-3d-cell-culture-an-essential-feature-for-in-vitro-toxicology
#10
Sophie A Lelièvre, Tim Kwok, Shirisha Chittiboyina
Three-dimensional cell culture has the potential to revolutionize toxicology studies by allowing human-based reproduction of essential elements of organs. Beyond the study of toxicants on the most susceptible organs such as liver, kidney, skin, lung, gastrointestinal tract, testis, heart and brain, carcinogenesis research will also greatly benefit from 3D cell culture models representing any normal tissue. No tissue function can be suitably reproduced without the appropriate tissue architecture whether mimicking acini, ducts or tubes, sheets of cells or more complex cellular organizations like hepatic cords...
March 30, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28344881/immunosurveillance-and-immunoediting-in-mmtv-pymt-induced-mammary-oncogenesis
#11
Emilie T E Gross, Semi Han, Prasantha Vemu, Carlos D Peinado, Martin Marsala, Lesley G Ellies, Jack D Bui
Evidence of cancer immunosurveillance and immunoediting processes has been primarily demonstrated in mouse models of chemically induced oncogenesis. Although these models are very tractable, they are characterized by high mutational loads that represent a minority of human cancers. In this study, we sought to determine whether cancer immunosurveillance and immunoediting could be demonstrated in a more clinically relevant oncogene-induced model of carcinogenesis, the MMTV-PyMT (PyMT) mammary carcinoma model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344868/langerhans-cells-and-nk-cells-cooperate-in-the-inhibition-of-chemical-skin-carcinogenesis
#12
Daniela Ortner, Christoph H Tripp, Kerstin Komenda, Sandrine Dubrac, Bernhard Zelger, Martin Hermann, Wolfgang Doppler, Piotr Z Tymoszuk, Louis Boon, Björn E Clausen, Patrizia Stoitzner
Tissue immunosurveillance is an important mechanism to prevent cancer. Skin treatment with the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), followed by the tumor promoter 12-O-tetra-decanoyl-phorbol-13-acetate (TPA), is an established murine model for squamous cell carcinoma (SCC). However, the innate immunological events occurring during the initiation of chemical carcinogenesis with DMBA remain elusive. Here, we discovered that natural killer (NK) cells and Langerhans cells (LC) cooperate to impair this oncogenic process in murine skin...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28335476/inhibition-of-neoplastic-transformation-and-chemically-induced-skin-hyperplasia-in-mice-by-traditional-chinese-medicinal-formula-si-wu-tang
#13
Mandy M Liu, Kevin M Huang, Steven Yeung, Andy Chang, Suhui Zhang, Nan Mei, Cyrus Parsa, Robert Orlando, Ying Huang
Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women's diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT's activity of cancer prevention...
March 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28333122/differences-in-the-bacteriome-of-smokeless-tobacco-products-with-different-oral-carcinogenicity-compositional-and-predicted-functional-analysis
#14
Nezar Noor Al-Hebshi, Fahd Ali Alharbi, Mohammed Mahri, Tsute Chen
Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in the chemical, but not the bacterial, constituents of these products. In this study, we explored the composition and function of the bacteriome in ST products from four countries using quantitative polymerase chain reaction (qPCR) and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4 × 10⁶) and highest in Yemeni shammah (6...
March 23, 2017: Genes
https://www.readbyqxmd.com/read/28331119/estimation-of-biological-effects-of-tritium
#15
Toshiyuki Umata
Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28327540/endocrine-disrupting-chemicals-and-endometrial-cancer-an-overview-of-recent-laboratory-evidence-and-epidemiological-studies
#16
REVIEW
Maddalena Mallozzi, Chiara Leone, Francesca Manurita, Filippo Bellati, Donatella Caserta
Background: Although exposure to endocrine disruptor compounds (EDCs) has been suggested as a contributing factor to a range of women's health disorders including infertility, polycystic ovaries and the early onset of puberty, considerable challenges remain in attributing cause and effect on gynaecological cancer. Until recently, there were relatively few epidemiological studies examining the relationship between EDCs and endometrial cancer, however, in the last years the number of these studies has increased...
March 22, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28322331/targeted-disruption-of-tc-ptp-in-the-proliferative-compartment-augments-stat3-and-akt-signaling-and-skin-tumor-development
#17
Hyunseung Lee, Mihwa Kim, Minwoo Baek, Liza D Morales, Ik-Soon Jang, Thomas J Slaga, John DiGiovanni, Dae Joon Kim
Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2(fl/fl)) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321044/investigation-of-the-early-response-genes-in-chemical-induced-renal-carcinogenicity-for-the-prediction-of-chemical-carcinogenicity-in-rats
#18
Hiroshi Matsumoto, Fumiyo Saito, Masahiro Takeyoshi
This study was designed to identify early-response genes of chemical-induced renal carcinogenicity for the prediction of chemical carcinogenicity in rats. We conducted a 28-day repeated-dose test in male Crl:CD (SD) rats with 12 carcinogens and 10 non-carcinogens as the training dataset, and five carcinogens and five non-carcinogens as the validation dataset. Renal gene expression profiles were analyzed by using a microarray. Fifteen candidate genes were selected from the gene expression profiles of the training dataset as genes that showed specific expression in response to carcinogens...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28317609/analysis-of-nitrite-and-nitrate-in-foods-overview-of-chemical-regulatory-and-analytical-aspects
#19
L Merino, U Örnemark, F Toldrá
In this chapter, several factors that should be considered for selecting and developing suitable analytical methods for determining nitrite/nitrate are presented. Nitrite and nitrate occurrence and suitability are a controversial issue. Nitrite is an approved additive considered a foremost curing ingredient for the preservation of meat products. Nitrate is a natural constituent of the human diet that, however, raises fears for its suggested potential harmfulness related to carcinogenesis and environmental contamination...
2017: Advances in Food and Nutrition Research
https://www.readbyqxmd.com/read/28316010/protective-effect-of-lactobacillus-casei-on-dmh-induced-colon-carcinogenesis-in-mice
#20
Cesar Antonio Irecta-Nájera, María Del Rosario Huizar-López, Josefina Casas-Solís, Patricia Castro-Félix, Anne Santerre
The administration of probiotics is a promising approach to reduce the prevalence of colon cancer, a multifactorial disease, with hereditary factors, as well as environmental lifestyle-related risk factors. Biogenic polyamines, putrescine, spermidine, and spermine are small cationic molecules with great roles in cell proliferation and differentiation as well as regulation of gene expression. Ornithine decarboxylase is the first rate-limiting enzyme for polyamine synthesis, and upregulation of ornithine decarboxylase activity and polyamine metabolism has been associated with abnormal cell proliferation...
March 18, 2017: Probiotics and Antimicrobial Proteins
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