How neighborhood environment modified the effects of power outages on multiple health outcomes in New York state?

Background: Although power outage (PO) is one of the most important consequences of increasing weather extremes and the health impact of POs has been reported previously, studies on the neighborhood environment underlying the population vulnerability in such situations are limited. This study aimed to identify dominant neighborhood environmental predictors which modified the impact of POs on multiple health outcomes in New York State.

Methods: We applied a two-stage approach.

Surface coatings alter transcriptional responses to silver nanoparticles following oral exposure.

Silver nanoparticles (AgNPs) are used in food packaging materials, dental care products and other consumer goods and can result in oral exposure. To determine whether AgNP coatings modulate transcriptional responses to AgNP exposure, we exposed mice orally to 20 nm citrate (cit)-coated AgNPs (cit-AgNPs) or polyvinylpyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) at a 4 mg/kg dose for 7 consecutive days and analyzed changes in the expression of protein-coding genes and long noncoding RNAs (lncRNAs), a new class of regulatory RNAs, in the liver. We identified unique and common expression signatures of protein-coding and lncRNA genes, altered biological processes and signaling pathways, and coding-non-coding gene interactions for cit-AgNPs and PVP-AgNPs.

Evaluation of Genotoxicity of Nanoparticles in Mouse Models.

Owing to new and unique properties, engineered nanoparticles (NPs) likely pose different risks than their constituent chemicals and these risks need to be understood. In particular, it is important to assess genotoxicity, since genotoxicity is a precursor to carcinogenicity. Here we describe a battery of tests for the assessment of genotoxicity of NPs in vivo in mice.

Pomegranate Extract Alters Breast Cancer Stem Cell Properties in Association with Inhibition of Epithelial-to-Mesenchymal Transition.

Cancer stem cells (CSCs) have become an important target population in cancer therapy and prevention due to their ability to self-renew, initiate tumors, and resist therapy. We examined whether pomegranate extract (PE) alters characteristics of breast CSCs. Ability to grow as mammospheres is a hallmark of breast CSCs.

Particle coatings but not silver ions mediate genotoxicity of ingested silver nanoparticles in a mouse model.

Incorporation of silver nanoparticles (AgNPs) in toothpaste, food containers, dietary supplements and other consumer products can result in oral exposure to AgNPs and/or silver ions (Ag) released from the surface of AgNPs. To examine whether ingestion of AgNPs or Ag results in genotoxic damage and whether AgNP coatings modulate the effect, we exposed mice orally to 20 nm citrate-coated AgNPs, polyvinylpyrrolidone (PVP)-coated AgNPs, silver acetate or respective vehicles at a 4 mg/kg dose (equivalent to 800x the EPA reference dose for Ag) for 7 days. Genotoxicity was examined in the systemic circulation and bone marrow at 1, 7, and 14 days post-exposure.

Pomegranate Intake Protects Against Genomic Instability Induced by Medical X-rays In Vivo in Mice.

Ionizing radiation (IR) is a well-documented human carcinogen. The increased use of IR in medical procedures has doubled the annual radiation dose and may increase cancer risk. Genomic instability is an intermediate lesion in IR-induced cancer.

Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU), the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA) moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs) may circumvent these limitations.

Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues.

Silver nanoparticles (AgNPs) are widely used in consumer and medical products. However, most AgNP toxicity data are based on in vitro studies. Only a few studies were performed in mammals and no studies systematically assessed cancer risk of AgNPs.

Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity.

Ataxia-telangiectasia is a genetic disorder associated with high incidence of B-cell lymphoma. Using an ataxia-telangiectasia mouse model, we compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress, and systemic leukocyte genotoxicity. High-throughput sequence analysis of rRNA genes identified mucosa-associated bacterial phylotypes that were colony-specific.

Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks.

Pomegranate extract (PE) inhibits the proliferation of breast cancer cells and stimulates apoptosis in MCF-7 breast cancer cells. While PE is a potent antioxidant, the present studies were conducted to examine the mechanisms of action of PE beyond antioxidation by studying cellular and molecular mechanisms underlying breast tumorigenesis. PE inhibited cell growth by inducing cell cycle arrest in G2 /M followed by the induction of apoptosis.

Effects of 1 GeV/nucleon ⁵⁶Fe particles on longevity, carcinogenesis and neuromotor ability in Atm-deficient mice.

As therapeutic uses of high-LET radiation become more prevalent and human space exploration continues to be a focus of NASA, it is important to understand the biological effects of high-LET radiation and the role of genetics in sensitivity to high-LET radiation. To study genetic susceptibility to radiation, we used mice deficient in Atm activity (AtmΔSRI). ATM is important in DNA repair, apoptosis and cell cycle regulation.

Genomic instability in mice is greater in Fanconi anemia caused by deficiency of Fancd2 than Fancg.

Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects, and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), nonhomologous end joining, and translesion synthesis (TLS).

Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice.

Titanium dioxide (TiO(2)) nanoparticles are manufactured worldwide in large quantities for use in a wide range of applications including pigment and cosmetic manufacturing. Although TiO(2) is chemically inert, TiO(2) nanoparticles can cause negative health effects, such as respiratory tract cancer in rats. However, the mechanisms involved in TiO(2)-induced genotoxicity and carcinogenicity have not been clearly defined and are poorly studied in vivo.

N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals.

Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it's ability to protect against gamma-ray-induced DNA strand breaks and/or DNA deletions in yeast and mammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy.

Effects of human Werner helicase on intrachromosomal homologous recombination mediated DNA deletions in mice.

Werner syndrome (WS) is a rare genetic disorder characterized by accelerated aging and aging-related diseases including cancer. WS is caused by autosomal recessive mutations in the WRN gene, which is involved in genome maintenance although precise functions of WRN are not well understood. To further investigate the role of WRN, we used transgenic mice over-expressing a human helicase mutant WRN gene (hMW).

Experimental antioxidant therapy in ataxia telangiectasia.

Ataxia telangiectasia (AT) is a rare genetic disorder characterized by immunodeficiency, early onset neurological degeneration, hypersensitivity to ionizing radiation and a high incidence of lymphoid cancers. The disease results from bi-allelic mutations in the AT mutated (ATM) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease.

Effects of antioxidants on cancer prevention and neuromotor performance in Atm deficient mice.

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by immunodeficiency, neurodegeneration and cancer. The disease results from bi-allelic mutations in the AT mutated (ATM) gene involved in cell cycle checkpoint control and repair of DNA double-strand breaks. Evidence has been accumulating that oxidative stress is associated with AT and may be involved in the pathogenesis of the disease.

Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes.

To shed light on the biological origins of sex differences in neural tube defects (NTDs), we examined Trp53-null C57BL/6 mouse embryos and neonates at 10.5 and 18.5 days post coitus (dpc) and at birth.

Involvement of homologous recombination in carcinogenesis.

DNA alterations of every type are associated with the incidence of carcinogenesis, often on the genomic scale. Although homologous recombination (HR) is an important pathway of DNA repair, evidence is accumulating that deleterious genomic rearrangements can result from HR. It therefore follows that HR events may play a causative role in carcinogenesis.

Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice.

Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations in the ATM gene, is characterized by a high incidence of lymphoid malignancies, neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity, and genomic instability. Evidence has been accumulating that ATM-deficient cells are in a continuous state of oxidative stress. A variety of markers of oxidative stress were detected in AT patients as well as Atm-deficient mice, used as an animal model of AT.

Developmental cell death in the liver and newborn lethality of Ku86 deficient mice suppressed by antioxidant N-acetyl-cysteine.

Repair of DNA double-strand breaks (DSBs) is essential for genome integrity and cell survival. Ku86 is involved in the repair of DNA DSBs by non-homologous end joining (NHEJ). Mice deficient in Ku86 show growth retardation, dwarfism, premature aging, and immunodeficiency.

Antioxidant N-acetyl cysteine reduces incidence and multiplicity of lymphoma in Atm deficient mice.

Hereditary human disorder ataxia telangiectasia (AT) is characterized by an extremely high incidence of lymphoid malignancies, neuromotor dysfunction, immunodeficiency and radiosensitivity. Cells from AT patients show genetic instability and a continuous state of oxidative stress. We examined the effect of long-term dietary supplementation with the thiol-containing antioxidant, N-acetyl-L-cysteine (NAC), on survival and cancer formation in Atm (AT-mutated) deficient mice, used as an animal model of AT.

Carcinogenic Cr(VI) and the nutritional supplement Cr(III) induce DNA deletions in yeast and mice.

Industrial Cr(VI) emissions contaminate drinking water sources across the U.S., and many people take Cr(III) nutritional supplements.