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1.
Oncogene ; 34(38): 4985-94, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25531321

RESUMO

Ionising radiation is a potent human carcinogen. Epidemiological studies have shown that adolescent and young women are at increased risk of developing breast cancer following exposure to ionising radiation compared with older women, and that risk is dose-dependent. Although it is well understood which individuals are at risk of radiation-induced breast carcinogenesis, the molecular genetic mechanisms that underlie cell transformation are less clear. To identify genetic alterations potentially responsible for driving radiogenic breast transformation, we exposed the human breast epithelial cell line MCF-10A to fractionated doses of X-rays and examined the copy number and cytogenetic alterations. We identified numerous alterations of c-MYC that included high-level focal amplification associated with increased protein expression. c-MYC amplification was also observed in primary human mammary epithelial cells following exposure to radiation. We also demonstrate that the frequency and magnitude of c-MYC amplification and c-MYC protein expression is significantly higher in breast cancer with antecedent radiation exposure compared with breast cancer without a radiation aetiology. Our data also demonstrate extensive intratumor heterogeneity with respect to c-MYC copy number in radiogenic breast cancer, suggesting continuous evolution at this locus during disease development and progression. Taken together, these data identify c-MYC as a radiosensitive locus, implicating this oncogenic transcription factor in the aetiology of radiogenic breast cancer.


Assuntos
Mama/efeitos da radiação , Genes myc , Tolerância a Radiação/genética , Mama/citologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Linhagem Celular , Variações do Número de Cópias de DNA , Feminino , Doença de Hodgkin/radioterapia , Humanos , Neoplasias Induzidas por Radiação/genética , Polimorfismo de Nucleotídeo Único , Doses de Radiação
2.
Eur J Clin Microbiol Infect Dis ; 18(4): 286-8, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10385018

RESUMO

Seven persons who attended the Glastonbury Music Festival were infected with Vero cytotoxin-producing Escherichia coli O157 and an eighth person had serological evidence of infection. Cases were reported from different parts of England. Patients were interviewed by telephone about clinical symptoms, festival attendance, camping details, food history, water exposure, and contact with mud and animals. The interviews identified no common food source, differing use of water sources and widely dispersed camping sites. Escherichia coli O157 strains from seven persons and from a cow belonging to a herd that had previously grazed the site all belonged to phage type 2 and possessed genes for Vero cytotoxin 2. Drug resistance and DNA-based tests showed that six patients were infected with strains indistinguishable from each other and from the bovine isolate. The most likely vehicle of infection was mud contaminated with Escherichia coli O157 from infected cattle.


Assuntos
Surtos de Doenças , Infecções por Escherichia coli/epidemiologia , Escherichia coli O157/isolamento & purificação , Adulto , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Reservatórios de Doenças , Inglaterra/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/transmissão , Infecções por Escherichia coli/veterinária , Escherichia coli O157/classificação , Fezes/microbiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Férias e Feriados , Humanos , Lactente , Música
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