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CHEMICAL CARCINOGENESIS

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https://www.readbyqxmd.com/read/29150404/stress-hormones-concentrations-in-the-normal-microenvironment-predict-risk-for-chemically-induced-cancer-in-rats
#1
Vitor Bonetti Valente, Flávia Alves Verza, Felipe Yudi Kabeya Lopes, Joana Zafalon Ferreira, Paulo Sérgio Patto Dos Santos, Maria Lúcia Marçal Mazza Sundefeld, Éder Ricardo Biasoli, Glauco Issamu Miyahara, Ana Maria Pires Soubhia, Mariza de Andrade, Sandra Helena Penha de Oliveira, Daniel Galera Bernabé
Evidence show that stress hormones can influence cancer progression, but its role in carcinogenesis is poorly understood. In this study, we used a new method based on oral carcinogenesis model in rats to test the hypothesis that physiological levels of stress hormones in the normal tissue microenvironment would have significant predictive value for chemically induced cancer occurrence. Male Wistar rats were submitted to a tongue biopsy for measuring not-stress induced levels of norepinephrine, corticosterone, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in the tissue before carcinogenic induction...
November 8, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29149346/novel-pathways-of-endocrine-disruption-through-pesticides-interference-with-human-mineralocorticoid-receptors
#2
Jianyun Zhang, Xin Huang, Hongling Liu, Weiping Liu, Jing Liu
Mineralocorticoid receptor (MR) is one member of the steroid receptor family. In addition to its important role in Na+/K+ homeostasis, MR is reported as a tumor-suppressor in carcinogenesis. So far, little was known about the ability of pesticides to interfere with MR. In this study, a total of 43 pesticides and/or metabolites were investigated for their potential effects on human MR. None of the tested pesticides exhibited MR agonistic potency, while 16 compounds showed antagonistic activities. Further investigations indicated that these 16 chemicals individually antagonized aldosterone-induced alkaline phosphatase expression in vascular smooth muscle cells and aldosterone-inhibited hepatocellular carcinoma cell proliferation at higher concentrations, and the mixture of these 16 pesticides at environmentally relevant concentrations significantly disrupted MR activity...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29145667/planarians-customize-their-stem-cell-responses-following-genotoxic-stress-as-a-function-of-exposure-time-and-regenerative-state
#3
An-Sofie Stevens, Annelies Wouters, Jan-Pieter Ploem, Nicky Pirotte, Andromeda Van Roten, Maxime Willems, Niels Hellings, Carmen Franken, Gudrun Koppen, Tom Artois, Michelle Plusquin, Karen Smeets
Aiming to in vivo characterise the responses of pluripotent stem cells and regenerative tissues to carcinogenic stress, we employed the highly regenerative organism Schmidtea mediterranea. Its broad regenerative capacities are attributable to a large pool of pluripotent stem cells, which are considered key players in the lower vulnerability towards chemically-induced carcinogenesis observed in regenerative organisms. S. mediterranea is, therefore, an ideal model to study pluripotent stem cell responses with stem cells residing in their natural environment...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29131934/methyl-dna-phosphate-adduct-formation-in-rats-treated-chronically-with-4-methylnitrosamino-1-3-pyridyl-1-butanone-and-enantiomers-of-its-metabolite-4-methylnitrosamino-1-3-pyridyl-1-butanol
#4
Bin Ma, Adam T Zarth, Erik S Carlson, Peter W Villalta, Pramod Upadhyaya, Irina Stepanov, Stephen S Hecht
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a powerful lung carcinogen in animal models and is considered a causative factor for lung cancer in tobacco users. NNK is stereoselectively and reversibly metabolized to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which is also a lung carcinogen. Both NNK and NNAL undergo metabolic activation by α-hydroxylation on their methyl groups to form pyridyloxobutyl and pyridylhydroxybutyl DNA base and phosphate adducts, respectively...
November 13, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29123614/the-roles-of-ros-in-cancer-heterogeneity-and-therapy
#5
REVIEW
Paulo Luiz de Sá Junior, Diana Aparecida Dias Câmara, Allan Saj Porcacchia, Pâmela Maria Moreira Fonseca, Salomão Doria Jorge, Rodrigo Pinheiro Araldi, Adilson Kleber Ferreira
Cancer comprises a group of heterogeneous diseases encompassing high rates of morbidity and mortality. Heterogeneity, which is a hallmark of cancer, is one of the main factors related to resistance to chemotherapeutic agents leading to poor prognosis. Heterogeneity is profoundly affected by increasing levels of ROS. Under low concentrations, ROS may function as signaling molecules favoring tumorigenesis and heterogeneity, while under high ROS concentrations, these species may work as cancer modulators due to their deleterious, genotoxic or even proapoptotic effect on cancer cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29110037/a-novel-integrated-in-vitro-carcinogenicity-test-to-identify-genotoxic-and-non-genotoxic-carcinogens-using-human-lymphoblastoid-cells
#6
Eleanor C Wilde, Katherine E Chapman, Leanne M Stannard, Anna L Seager, Katja Brüsehafer, Ume-Kulsoom Shah, James A Tonkin, M Rowan Brown, Jatin R Verma, Ann T Doherty, George E Johnson, Shareen H Doak, Gareth J S Jenkins
Human exposure to carcinogens occurs via a plethora of environmental sources, with 70-90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment...
November 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29109131/carbidopa-a-selective-ah-receptor-modulator-sahrm
#7
Stephen Safe
The aryl hydrocarbon receptor (AhR) was discovered as the intracellular receptor that bound with high affinity to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the AhR is required for mediating the toxicity induced by TCDD. Subsequent studies show that the AhR binds structurally diverse chemicals including plant-derived compounds that promote health and several AhR-active pharmaceuticals that exhibit anticancer activity. In this issue, there is a report that carbidopa, a drug used for treating Parkinson's disease, is also an AhR ligand, and this compound inhibits pancreatic cancer cell and tumor growth...
November 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29074535/flaxseed-consumption-inhibits-chemically-induced-lung-tumorigenesis-and-modulates-expression-of-phase-ii-enzymes-and-inflammatory-cytokines-in-a-j-mice
#8
Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Ralph Pietrofesa, Athena Zuppa, Ganesh Moorthy, Neil Dyer, Melpo Christofidou-Solomidou, Katie M Reindl
Flaxseed consumption is associated with reduced oxidative stress and inflammation in lung injury models, and has shown anti-cancer effects for breast and prostate tissues. However, the chemopreventive potential of flaxseed remains unexplored for lung cancer. In this study, we investigated the effect of flaxseed on tobacco smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice exposed to NNK were fed a control diet or a 10% flaxseed-supplemented diet for 26 weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78%) and multiplicity, with an average of 2...
October 26, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29072741/an-interaction-network-approach-to-study-the-correlation-between-endocrine-disrupting-chemicals-and-breast-cancer
#9
Andrea Polo, Chiara Nittoli, Anna Crispo, Teresa Langastro, Stefania Cocco, Lorella Severino, Michelino De Laurentiis, Gennaro Ciliberto, Maurizio Montella, Alfredo Budillon, Susan Costantini
Endocrine disrupting chemicals (EDCs) are natural or synthetic exogenous substances affecting human health. Although present at low concentrations in the environment, they can cause a broad range of negative effects on the endocrine functions by mimicking the action of steroid hormones due to their structural similarity. Hormonal unbalance can play an important role in carcinogenesis at any stage of disease. In the case of the breast cancer, EDCs directly affect the transformation of normal breast cells into cancer cells by interfering with hormonal regulation and by inducing the alteration of factors that regulate gene expression...
October 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/29071010/error-prone-and-error-free-translesion-dna-synthesis-over-site-specifically-created-dna-adducts-of-aryl-hydrocarbons-3-nitrobenzanthrone-and-4-aminobiphenyl
#10
REVIEW
Takashi Yagi, Yoshihiro Fujikawa, Tomoko Sawai, Takeji Takamura-Enya, Sayoko Ito-Harashima, Masanobu Kawanishi
Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP), acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form bulky DNA adducts when absorbed by mammalian cells. These chemicals are metabolically activated to reactive forms in mammalian cells and preferentially get attached covalently to the N(2) or C8 positions of guanine or the N(6) position of adenine. The proportion of N(2) and C8 guanine adducts in DNA differs among chemicals. Although these adducts block DNA replication, cells have a mechanism allowing to continue replication by bypassing these adducts: translesion DNA synthesis (TLS)...
October 2017: Toxicological Research
https://www.readbyqxmd.com/read/29068672/effects-of-black-raspberry-extract-and-berry-compounds-on-repair-of-dna-damage-and-mutagenesis-induced-by-chemical-and-physical-agents-in-human-oral-leukoplakia-and-rat-oral-fibroblasts
#11
Joseph Guttenplan, Kun-Ming Chen, Yuan-Wan Sun, Braulio Lajara, Nora Ae Shalaby, Wieslawa Kosinska, Gabrielle Benitez, Krishne Gowda, Shantu Amin, Gary David Stoner, Karam El-Bayoumy
Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of systems, with most studies focusing on progression. Previously we reported that an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo[a,l]pyrene dihydrodiol (DBP-diol) induced DNA adducts and inhibited DBP-diol and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast cell line, suggesting a role for BRB in the inhibition of initiation of carcinogenesis. Here we extend this work to protection by BE, against DNA adduct formation induced by dibenzo[a,l]pyrene (DBP) in a human oral leukoplakia cell line (MSK) and to second carcinogen, UV light...
October 25, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29065504/a-mini-review-of-reactive-oxygen-species-in-urological-cancer-correlation-with-nadph-oxidases-angiogenesis-and-apoptosis
#12
REVIEW
Yasuyoshi Miyata, Tomohiro Matsuo, Yuji Sagara, Kojiro Ohba, Kaname Ohyama, Hideki Sakai
Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and NADPH oxidases (NOXs), which are one of the most important sources of ROS. Oxidative stress plays important roles in the etiologies, pathological mechanisms, and treatment strategies of vascular diseases. Additionally, oxidative stress affects mechanisms of carcinogenesis, tumor growth, and prognosis in malignancies. Nearly all solid tumors show stimulation of neo-vascularity, termed angiogenesis, which is closely associated with malignant aggressiveness...
October 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29056487/transcriptome-profiling-of-red-swamp-crayfish-procambarus-clarkii-hepatopancreas-in-response-to-lipopolysaccharide-lps-infection
#13
Miao Zhou, Muhammad Nadeem Abbas, Saima Kausar, Cheng-Xi Jiang, Li-Shang Dai
The RNA-sequencing followed by de novo assembly generated 61,912 unigene sequences of P. clarkii hepatopancreas. Comparison of gene expression between LPS challenged and PBS control samples revealed 2552 differentially expressed genes (DEGs). Of these sequences, 1162 DEGs were differentially up-regulated and 1360 DEGs differentially down-regulated. The DEGs were then annotated against gene ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Some immune-related pathways such as PPAR signaling pathway, lysosome, Chemical carcinogenesis, Peroxisome were predicted by canonical pathways analysis...
October 19, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29054680/phosphorylation-of-protein-phosphatase-2a-facilitated-an-early-stage-of-chemical-carcinogenesis
#14
Yuji Ishii, Ken Kuroda, Kohei Matsushita, Yuh Yokoo, Shinji Takasu, Aki Kijima, Takehiko Nohmi, Kumiko Ogawa, Takashi Umemura
Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates cell signaling pathways. Its inactivation is correlated with tumor malignancy, possibly due to the effects on cell differentiation and malignant cell transformation. Therefore, it has been noted that PP2A could be a promising target for cancer therapy. In our previous study of the hepatocarcinogen estragole (ES), cell proliferation may be required to convert ES-specific DNA adducts to mutations. To explore the trigger for cell proliferation, gpt delta rats were administered ES by gavage at doses of 3, 30 and 300mg/kg/day for 4weeks...
October 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29050278/identification-of-core-genes-and-outcome-in-gastric-cancer-using-bioinformatics-analysis
#15
Chenhua Sun, Qi Yuan, Dongdong Wu, Xiaohu Meng, Baolin Wang
Gastric cancer (GC) is a common malignant neoplasm of gastrointestinal tract. We chose gene expression profile of GSE54129 from GEO database aiming to find key genes during the occurrence and development of GC. 132 samples, including 111 cancer and 21 normal gastric mucosa epitheliums, were included in this analysis. Differentially expressed genes (DEGs) between GC patients and health people were picked out using GEO2R tool, then we performed gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using The Database for Annotation, Visualization and Integrated Discovery (DAVID)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046336/pp2a-inactivation-mediated-by-ppp2r4-haploinsufficiency-promotes-cancer-development
#16
Ward Sents, Bob Meeusen, Petar Kalev, Enrico Radaelli, Xavier Sagaert, Eline Miermans, Dorien Haesen, Caroline Lambrecht, Mieke Dewerchin, Peter Carmeliet, Jukka Westermarck, Anna Sablina, Veerle Janssens
Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular PP2A inhibitors. Here we identify a novel genetic mechanism by which PP2A function is recurrently affected in human cancer, involving haploinsufficiency of PPP2R4, a gene encoding the cellular PP2A activator PTPA. Notably, up to 70% of cancer patients showed a heterozygous deletion or missense mutations in PPP2R4 Cancer-associated PTPA mutants exhibited decreased abilities to bind the PP2A-C subunit or activate PP2A and failed to reverse the tumorigenic phenotype induced by PTPA suppression, indicating they function as null alleles...
October 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/29026063/morphological-transformation-induced-by-silver-nanoparticles-in-balb-c-3t3-a31-1-1-mouse-cell-model-to-evaluate-in-vitro-carcinogenic-potential
#17
Wun Hak Choo, Byeonghak Moon, Sulhwa Song, Seung Min Oh
Carcinogenesis is a complex process involving in genotoxic and non-genotoxic pathways. Carcinogenic potential of AgNPs has been predicted by genotoxic effects using several in vitro and in vivo models. However, there is no little information on non-genotoxic effects of AgNPs for carcinogenesis. In vitro cell transformation assay (CTA) can provide specific and sensitive evidence to predict the tumorigenic potential of a chemical, which cannot be supplied by genotoxicity testing. Therefore, we carried out CTA in Balb/c 3T3 A31-1-1 cells to evaluate the carcinogenic potential of silver nanoparticle (AgNPs)...
October 7, 2017: Environmental Health and Toxicology
https://www.readbyqxmd.com/read/29020440/influence-of-dna-lesions-on-polymerase-mediated-dna-replication-at-single-molecule-resolution
#18
Hailey L Gahlon, Louis J Romano, David Rueda
Faithful replication of DNA is a critical aspect in maintaining genome integrity. DNA polymerases are responsible for replicating DNA, and high-fidelity polymerases do this rapidly and at low error rates. Upon exposure to exogenous or endogenous substances, DNA can become damaged and this can alter the speed and fidelity of a DNA polymerase. In this instance, DNA polymerases are confronted with an obstacle that can result in genomic instability during replication, for example, by nucleotide misinsertion or replication fork collapse...
October 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28987728/environmental-chemicals-and-breast-cancer-an-updated-review-of-epidemiological-literature-informed-by-biological-mechanisms
#19
REVIEW
Kathryn M Rodgers, Julia O Udesky, Ruthann A Rudel, Julia Green Brody
BACKGROUND: Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. OBJECTIVE: For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development...
October 6, 2017: Environmental Research
https://www.readbyqxmd.com/read/28985473/red-clover-aryl-hydrocarbon-receptor-ahr-and-estrogen-receptor-er-agonists-enhance-genotoxic-estrogen-metabolism
#20
Tareisha L Dunlap, Caitlin E Howell, Nita Mukand, Shao-Nong Chen, Guido F Pauli, Birgit M Dietz, Judy L Bolton
Many women consider botanical dietary supplements (BDSs) as safe alternatives to hormone therapy for menopausal symptoms. However, the effect of BDSs on breast cancer risk is largely unknown. In the estrogen chemical carcinogenesis pathway, P450 1B1 metabolizes estrogens to 4-hydroxylated catechols, which are oxidized to genotoxic quinones that initiate and promote breast cancer. In contrast, P450 1A1 catalyzed 2-hydroxylation represents a detoxification pathway. The current study evaluated the effects of red clover, a popular BDS used for women's health, and its isoflavones, biochanin A (BA), formononetin (FN), genistein (GN), and daidzein (DZ), on estrogen metabolism...
October 19, 2017: Chemical Research in Toxicology
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