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stem cell carcinogenic

Jana Tomc, Katja Kološa, Bojana Žegura, Urška Kamenšek, Barbara Breznik, Tamara Lah Turnšek, Metka Filipič
The problem of the currently used routine genotoxicity tests is relatively low predictivity of in vitro tests for in vivo genotoxicity and carcinogenicity. An important reason is considered to be inadequate expression of xenobiotic-metabolizing enzymes in indicator cell lines. The aim of our study was to generate metabolically active differentiated hepatic progenies (hDHP) from human adipose tissue-derived mesenchymal stem cells (hASC) for genotoxicity testing. hDHP, generated using a three-step hepatic differentiation procedure, expressed hepatic properties such as glycogen storage and albumin secretion...
March 16, 2018: Archives of Toxicology
Yesol Bak, Hui-Joo Jang, Jong-Woon Shin, Soo-Jin Kim, Hyun Woo Chun, Ji-Hye Seo, Su-Hyun No, Jung-Il Chae, Dong Hee Son, Seung Yeoun Lee, Jintae Hong, Do-Young Yoon
The carcinogenicity of chemicalsin the environment is a major concern. Recently, numerous studies have attempted to develop methods for predicting carcinogenicity including rodent and cell-based approaches. However, rodent carcinogenicity tests for evaluating the carcinogenic potential of a chemical to humans are time-consuming and costly. This study focused on the development of an alternative method for predicting carcinogenicity using quantitative PCR (qPCR) and colon cancer stem cells.A toxicogenomic method,mRNA profiling, is useful for predicting carcinogenicity...
March 15, 2018: Journal of Microbiology and Biotechnology
Clara B García-Calderón, José Antonio Bejarano-García, Isabel Tinoco-Gago, María José Castro, Paula Moreno-Gordillo, José I Piruat, Teresa Caballero-Velázquez, José A Pérez-Simón, Iván V Rosado
Metabolically reactive formaldehyde is a genotoxin and a carcinogen. Mice lacking the main formaldehyde-detoxifying gene Adh5 combined with the loss of the Fanconi anemia (FA) DNA repair pathway rapidly succumbed to bone marrow failure (BMF) primarily due to the extensive ablation of the hematopoietic stem cell (HSC) pool. However, the mechanism by which formaldehyde mediates these toxic effects is still unknown. We uncover a detrimental role of tetrahydrofolic acid (THF) in cells lacking Adh5 or the FA repair pathway...
March 6, 2018: Cell Death and Differentiation
Elżbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
HOTAIR (HOX transcript antisense RNA) plays a critical role in chromatin dynamics through the interaction with histone modifiers resulting in transcriptional gene silencing. The promoter of the HOTAIR gene contains multiple estrogen response elements (EREs) and is transcriptionally activated by estradiol in estrogen receptor-positive breast cancer cells. HOTAIR competes with BRCA1, a critical protein in breast cancer and is a critical regulator of genes involved in epithelial-to-mesenchymal transition. It mediates an oncogenic action of c-Myc, essential for breast carcinogenesis...
November 3, 2017: International Journal of Molecular Sciences
Henning Hintzsche, Gracia Montag, Helga Stopper
For mutagenicity testing, primary lymphocytes or mammalian cell lines are employed. However, the true target for carcinogenic action of mutagenic chemicals may be stem cells. Since hematopoietic cancers induced by chemical agents originate at the hematopoietic stem cell (HSC) stage and since one of the side effects of chemotherapeutic cancer treatment is the induction of secondary tumors, often leukemias, HSC may be a suitable cell system. We compared the sensitivity of HSC with the genotoxicity testing cell line TK6 for chromosomal mutations...
February 20, 2018: Scientific Reports
Cinzia Borgogna, Carlotta Olivero, Simone Lanfredini, Federica Calati, Marco De Andrea, Elisa Zavattaro, Paola Savoia, Elena Trisolini, Renzo Boldorini, Girish K Patel, Marisa Gariglio
Many malignancies that occur in high excess in kidney transplant recipients (KTRs) are due to viruses that thrive in the setting of immunosuppression. Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR, has been associated with skin infection by human papillomavirus (HPV) from the beta genus. In this report, we extend our previous investigation aimed at identifying the presence of active β-HPV infection in skin tumors from KTRs through detection of viral protein expression. Using a combination of antibodies raised against the E4 and L1 proteins of the β-genotypes, we were able to visualize infection in five tumors [one keratoacanthoma (KA), three actinic keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from two patients who had been both transplanted twice, had developed multiple KCs, and presented with a long history of immunosuppression (>30 years)...
2018: Frontiers in Microbiology
Hossein Ranjbaran, Saeid Abediankenari, Masoud Mohammadi, Narjes Jafari, Alireza Khalilian, Zahra Rahmani, Marzei Momeninezhad Amiri, Pirooz Ebrahimi
Wharton`s jelly-derived mesenchymal stem cells (WJ-MSCs), have a high proliferation valency and they do not produce teratogen or carcinogen after subsequent transplantation. They are known as regenerative medicine. Thus more research is needed on the isolation and characterization of mesenchymal stem cells. In this experimental study, we obtained Wharton's jelly tissues from mothers during normal vaginal delivery, after obtaining their informed consent. Mesenchymal stem cells were isolated from cultured Wharton`s jelly, cultured, and were then examined for their proliferation, immunophenotypes, and differentiation capacities...
January 2018: Acta Medica Iranica
Shao-Feng Yang, Ran Ma, Li-Li Pan, Jing Cao, Nan Sheng
Gastric cancer is associated with a high mortality rate, with the development of gastric cancer stem cells underlying this. Gastric cancer stem cells are responsible for tumor initiation, progression and recurrence. However, the link between gastric cancer and gastric cancer stem cells remains to be fully understood. Murine models mimic a human microenvironment more accurately than in vitro studies and are useful models for understanding the behavior of different markers. The present study compared the expression of cluster of differentiation 44 (CD44), a stem cell marker, with the expression of other cancer-associated markers, including Raf kinase inhibitor protein (RKIP) and peroxiredoxin 2, in different pathological conditions of gastric cancer development using histological, immunohistological and western blot analyses...
March 2018: Oncology Letters
Osamu Toyoshima, Chizu Tanikawa, Ryuta Yamamoto, Hidenobu Watanabe, Hiroharu Yamashita, Kosuke Sakitani, Shuntaro Yoshida, Michiaki Kubo, Keitaro Matsuo, Hidemi Ito, Kazuhiko Koike, Yasuyuki Seto, Koichi Matsuda
SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10-5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer...
January 9, 2018: Oncotarget
Zhishan Wang, Jianjun Wu, Brock Humphries, Kazuya Kondo, Yiguo Jiang, Xianglin Shi, Chengfeng Yang
While hexavalent chromium [Cr(VI)] is generally considered as a genotoxic environmental carcinogen, studies showed that Cr(VI) exposure also causes epigenetic changes. However, whether Cr(VI)-caused epigenetic dysregulations plays an important role in Cr(VI) carcinogenicity remain largely unknown. The aim of this study was to determine if chronic low dose Cr(VI) exposure causes epigenetic changes, the underlying mechanism and whether chronic low dose Cr(VI) exposure-caused epigenetic dysregulation contributes causally to Cr(VI)-induced cancer stem cell (CSC)-like property and cell transformation...
January 29, 2018: Toxicology and Applied Pharmacology
Nouf Abdulkareem Omer Alkharashi, Vaiyapuri Subbarayan Periasamy, Jegan Athinarayanan, Ali A Alshatwi
Cd is a hazardous substance and carcinogen that is present in the environment; it is known to cause toxic effects in living organisms. Sulforaphane is a naturally available phytochemical with antioxidant, anti-inflammatory, and anticarcinogenic properties. However, the effects of sulforaphane on Cd toxicity in human mesenchymal stem cells (hMSCs) are unknown. In the present study, we investigated the molecular mechanisms of the effects of sulforaphane on Cd toxicity in hMSCs by using MTT assays, acridine orange/ethidium bromide staining, Hoechst staining, LysoRed staining, assessment of mitochondrial membrane potential, and gene expression analysis...
January 27, 2018: Environmental Science and Pollution Research International
Wen-Jyi Lo, Chiao-Lin Lin, Yu-Chien Chang, Li-Yuan Bai, Chen-Yuan Lin, Ji-An Liang, Long-Yuan Li, Ling-Min Chao, Chang-Fang Chiu, Chuan-Mu Chen, Su-Peng Yeh
Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control...
January 18, 2018: Annals of Hematology
Alvarez-Salas, Zamora-Contreras
BACKGROUND: The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. OBJECTIVE: Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. METHODS: Pre-let-7 levels were determined by RTqPCR...
January 15, 2018: MicroRNA
Kostiantyn Dreval, Volodymyr Tryndyak, Iryna Kindrat, Nathan C Twaddle, Orish Ebere Orisakwe, Thilak K Mudalige, Frederick A Beland, Daniel R Doerge, Igor P Pogribny
Inorganic arsenic is a human carcinogen associated with several types of cancers, including liver cancer. Inorganic arsenic has been postulated to target stem cells, causing their oncogenic transformation. This is proposed to be one of the key events in arsenic-associated carcinogenesis; however, the underlying mechanisms for this process remain largely unknown. To address this question, human hepatic HepaRG cells, at progenitor and differentiated states, were continuously treated with a non-cytotoxic concentration of 1 μM sodium arsenite (NaAsO2)...
January 2, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Emilio Guillén-Mancina, José Manuel Calderón-Montaño, Miguel López-Lázaro
Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially exerts a local carcinogenic effect. Recent findings indicate that the risk of cancer in a tissue is strongly correlated with the number of stem cell divisions accumulated by the tissue; the accumulation of stem cell divisions leads to the accumulation of cancer-promoting errors such as mutations occurring during DNA replication...
December 27, 2017: Drug and Alcohol Dependence
Yinghua Lv, Pengfei Zhang, Jiayin Guo, Zhendong Zhu, Xueliang Li, Dazhong Xu, Wenxian Zeng
Given the potential biological functions of spermatogonial stem cells (SSCs) in spermatogenesis and in delivering parental genetic information to the next generation, how these cells respond to environmental toxins and carcinogens should be investigated. We examined the toxic effect of hexavalent chromium (Cr(VI)) on global histone modifications and apoptotic signaling pathways in SSCs. We determined the effect of melatonin, one of the most powerful endogenous free radical scavengers and wide-spectrum antioxidants, in protecting SSCs from Cr(VI)-induced apoptosis and global histone modification by Western blot analysis...
December 28, 2017: Toxicology and Applied Pharmacology
Ángel C Roman, José M Carvajal-Gonzalez, Jaime M Merino, Sonia Mulero-Navarro, Pedro M Fernández-Salguero
The aryl hydrocarbon receptor (AhR) is well-known for its major contributions to the cellular responses against environmental toxins and carcinogens. Notably, AhR has also emerged as a key transcription factor controlling many physiological processes including cell proliferation and apoptosis, differentiation, adhesion and migration, pluripotency and stemness. These novel functions have broadened our understanding of the signaling pathways and molecular intermediates interacting with AhR under both homeostatic and pathological conditions...
December 16, 2017: Pharmacology & Therapeutics
Emma Åkerlund, Francesca Cappellini, Sebastiano Di Bucchianico, Shafiqul Islam, Sara Skoglund, Remco Derr, Inger Odnevall Wallinder, Giel Hendriks, Hanna L Karlsson
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2 . We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ-H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay)...
April 2018: Environmental and Molecular Mutagenesis
Ross A Johnson, Phillip A Conklin, Michelle Tjahjadi, Victor Missirian, Ted Toal, Siobhan M Brady, Anne B Britt
In Arabidopsis, DNA damage-induced programmed cell death is limited to the meristematic stem cell niche and its early descendants. The significance of this cell-type-specific programmed cell death is unclear. Here, we demonstrate in roots that it is the programmed destruction of the mitotically compromised stem cell niche that triggers its regeneration, enabling growth recovery. In contrast to wild-type plants, sog1 plants, which are defective in damage-induced programmed cell death, maintain the cell identities and stereotypical structure of the stem cell niche after irradiation, but these cells fail to undergo cell division, terminating root growth...
February 2018: Plant Physiology
Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection...
December 6, 2017: BMC Gastroenterology
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