RESUMO
BACKGROUND: Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response. PRINCIPAL FINDINGS: Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed. CONCLUSIONS/SIGNIFICANCE: Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted.
Assuntos
Dano ao DNA , DNA Circular/metabolismo , Instabilidade Genômica , Neoplasias/genética , Transporte Biológico , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Quebras de DNA , Proteínas de Ligação a DNA , Humanos , Espaço Intracelular/metabolismo , Células MCF-7 , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismoRESUMO
OBJECTIVE: We report a male patient with ovotesticular disorder of sex development (OTDSD), resulting from structurally abnormal Y chromosome. CASE REPORT: A 3-year-old boy was admitted to the Surgical Pediatric Department for masculinizing reconstruction. He had a clitorophallus, bifid scrotum, perineal hypospadias and bilateral impalpable gonads. Pelvic ultrasound and laparoscopy showed a uterus and two gonads with primary ovarian follicles. Chromosome analysis detected a mos 47,XX,mar/46,XX karyotype. Complex genetic evaluation revealed that the marker was Yp isochromosome. Surgical care included a feminizing genitoplasty and separation of the gonads with total excision of testicular tissue. CONCLUSIONS: The presented case emphasizes the importance of a systematic approach to the investigation and management of the patients with ovotesticular DSD. It also raises the important issue about gender reassignment in intersex individuals in mid-childhood.
