61 research outputs found
Perfluorohexane sulfonate (PFHxS) and a mixture of endocrine disrupters reduce thyroxine levels and cause antiandrogenic effects in rats
Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS+EDmix (n=5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25mg PFHxS/kg plus EDmix (n=13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Germline genetic modification, CRSIPR, and human identity: Can genetics turn you into someone else?
Developing a risk based engineering manager competency standard for oil and gas EPC project in Indonesia
Vachellia erioloba dynamics over 38 years in the Kalahari Gemsbok National Park, South Africa
U.S. PET/CT and Gamma Camera Diagnostic Reference Levels and Achievable Administered Activities for Noncardiac Nuclear Medicine Studies
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