Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzoapyrene and 2-Amino-1-Methyl-6-Phenylimidazo4,5-bpyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens

Conclusions: Mixtures of these genotoxic chemicals produced mutation responses that differed from expectations for additive effects of the individual chemicals. The increase in MF for some combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, and the non-monotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process. Citation: David R, Ebbels T, Gooderham N. Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens. Environ Health Perspect; http://dx.doi.org/10.1289/ehp.1409557. Received: 4 December 2014 Accepted: 16 June 2015 Advance Publication: 19 June 2015 EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the c...
Source: EHP Research - Category: Environmental Health Authors: Tags: Research Article Source Type: research

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ConclusionOur results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA ‐seq.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Conclusions: PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been de...
Source: Redox Report : communications in free radical research - Category: Biochemistry Authors: Tags: Redox Rep Source Type: research
verina Pacifico The weak but noteworthy presence of (poly)phenols in hemp seeds has been long overshadowed by the essential polyunsaturated fatty acids and digestible proteins, considered responsible for their high nutritional benefits. Instead, lignanamides and their biosynthetic precursors, phenylamides, seem to display interesting and diverse biological activities only partially clarified in the last decades. Herein, negative mode HR-MS/MS techniques were applied to the chemical investigation of a (poly)phenol-rich fraction, obtained from hemp seeds after extraction/fractionation steps. This extract contained phenyl...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell–dependent manner. VitC not only enhances the cytotoxic activity of ad...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
This study offers a powerful network-based methodology for identification of candidate therapeutic pathways that target tumor vulnerabilities and prioritization of potential pharmacogenomics biomarkers for development of personalized cancer medicine.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
ConclusionThe potential therapeutic value of fluzoparib for increasing the radiation sensitivity of NSCLC is well confirmed. Moreover, our findings of high mutation frequencies among HR genes suggest that PARP1 inhibition may be an effective treatment strategy for advanced non-small cell lung cancer patients.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We present the action mode of DDR molecule inhibitors in preclinical studies and clinical cancer therapy, including monotherapy and combination therapy with chemotherapeutic drugs or checkpoint suppression therapy. PMID: 32091326 [PubMed - as supplied by publisher]
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
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