The exposure to high doses of ionizing radiation (>5Gy) is unequivocally associated with increased cancer risk. However, there is substantial experimental evidence showing that in response to low doses of ionizing radiation (LDR: <100mGy), cells and organisms are benefitted with delayed ageing, improved immunity and reduced cancer growth. These intriguing findings have proposed the “Radiation Hormesis” hypothesis. Herein, I studied the senescence effects of LDR exposure to normal human HFL1 cells and examined transcriptional changes. I found that HFL1 cells exposed to 10 mGy of gamma radiation had delayed senescence measured at 12 weeks post-irradiation compared to unirradiated cells. Through qPCR array analysis, I found that genes involved in human cellular senescence functions are differentially regulated in 10 mGy exposed cells at 12 weeks compared to 1-week post-exposure. A nucleolar protein, SIRT7, that belongs to the family of proteins called Sirtuins with known roles in aging, was found to be upregulated transcriptionally in LDR-exposed HFL1 cells. Knocking out SIRT7 protein significantly accelerated senescence in HFL1 cells suggesting a direct role of SIRT7 in the deceleration of senescence and potentially in mediating radiation hormesis. Furthermore, overexpression of the HRAS oncogene strongly accelerated senescence in HFL1 cells through gene expression of cell cycle regulators and checkpoint proteins. Together, my studies revealed that LDR induces unique transcriptional changes resulting in a potentially radio adaptive protective cellular response. I also discuss the HRAS overexpression system as a time-efficient cellular model that could be used to more rapidly study the effect of LDR on senescence using primary cultures.

Os lipídios microbianos apresentam composição similar aos óleos vegetais, e tem despertado o interesse de muitos pesquisadores, uma vez que podem suprir a demanda por óleos e gorduras. Além disso, estudos demonstram que ao submeter um microrganismo a baixas doses de radiação gama, estímulos são promovidos, podendo aumentar a função, a resistência celular, e o crescimento. Objetivou-se com esse estudo: avaliar os efeitos de baixas doses de radiação gama no crescimento e na síntese lipídica de Yarrowia lipolytica. A levedura foi submetida às doses de: (controle) 0,3; 0,5; 0,75; 1,0; 1,25 e 2,5 kGy de radiação gama, sob taxa de dose de 0,259 kGy/h. Foi utilizada câmara de Neubauer para determinação da viabilidade celular da levedura. Uma curva de crescimento e outra de sobrevivência foi determinada por densidade óptica em um espectrofotômetro. Posteriormente, a levedura foi inoculada em meio composto por xarope de cana-de-açúcar e vinhaça, e incubada por 7, 14 e 21 dias para a obtenção da biomassa seca, por liofilização, e da síntese lipídica, por metodologia de extração. A irradiação não interferiu na produção de biomassa seca, no crescimento e na sobrevivência da levedura Y. lipolytica. O período de incubação afetou a produção final de biomassa, sendo a maior produção obtida no 14° dia (13,46 g/L). Para os resultados de síntese lipídica, observou-se interferência na produção final, durante 21 dias de incubação e dose de 0,5 kGy, com produção de 4,17 g/L (34,94%). Conclui-se que não foi observado o efeito hormético durante as análises de crescimento, sobrevivência e produção de biomassa, quando submetidas às doses de radiação. Este efeito foi observado apenas durante a síntese lipídica, quando avaliadas as junções entre dose de radiação e período de incubação / Microbial lipids present similar composition to vegetable oils and has aroused great interest among researchers. In addition, studies show that by submitting a microorganism to low doses of gamma radiation, stimuli are promoted, which could increase the function, cell resistance, and the growth. Therefore, this study aimed to evaluate the effects of low doses of gamma radiation on the growth and lipid synthesis of Yarrowia lipolytica. The yeast received irradiation doses of: (control); 0.3; 0.5; 0.75; 1.0; 1.25 and 2.5 kGy gamma radiation dose rate in 0.259 kGy/h. Neubauer Chamber was used to analyze cell viability of the yeast. A growth curve and survival curve was determined by spectrophotometry. Then, the yeast was inoculated in the medium composed of syrup sugarcane and vinasse and incubated for 7, 14 and 21 days for the obtaining of dry biomass, by lyophilization, and lipid synthesis, by extraction methodology. The low doses of irradiation had no effect on the growth, survival, and production of dry biomass of Y. lipolytica. For the incubation periods, there was interference in the final production; the highest production was obtained on day 14 (13.46 g/L). The results for lipid synthesis revealed interference with the final production of lipids, being better at a dose of 0.5 kGy to 21 days incubation with yield of 4.17 g/L (34.94%). In conclusion, the low doses of irradiation had no effect on the growth, survival and biomass production of Y. lipolytica. Hormetic effect was observed only in the lipid synthesis, when the radiation dose was associated with the incubation time

Os lipídios microbianos apresentam composição similar aos óleos vegetais, e tem despertado o interesse de muitos pesquisadores, uma vez que podem suprir a demanda por óleos e gorduras. Além disso, estudos demonstram que ao submeter um microrganismo a baixas doses de radiação gama, estímulos são promovidos, podendo aumentar a função, a resistência celular, e o crescimento. Objetivou-se com esse estudo: avaliar os efeitos de baixas doses de radiação gama no crescimento e na síntese lipídica de Yarrowia lipolytica. A levedura foi submetida às doses de: (controle) 0,3; 0,5; 0,75; 1,0; 1,25 e 2,5 kGy de radiação gama, sob taxa de dose de 0,259 kGy/h. Foi utilizada câmara de Neubauer para determinação da viabilidade celular da levedura. Uma curva de crescimento e outra de sobrevivência foi determinada por densidade óptica em um espectrofotômetro. Posteriormente, a levedura foi inoculada em meio composto por xarope de cana-de-açúcar e vinhaça, e incubada por 7, 14 e 21 dias para a obtenção da biomassa seca, por liofilização, e da síntese lipídica, por metodologia de extração. A irradiação não interferiu na produção de biomassa seca, no crescimento e na sobrevivência da levedura Y. lipolytica. O período de incubação afetou a produção final de biomassa, sendo a maior produção obtida no 14° dia (13,46 g/L). Para os resultados de síntese lipídica, observou-se interferência na produção final, durante 21 dias de incubação e dose de 0,5 kGy, com produção de 4,17 g/L (34,94%). Conclui-se que não foi observado o efeito hormético durante as análises de crescimento, sobrevivência e produção de biomassa, quando submetidas às doses de radiação. Este efeito foi observado apenas durante a síntese lipídica, quando avaliadas as junções entre dose de radiação e período de incubação / Microbial lipids present similar composition to vegetable oils and has aroused great interest among researchers. In addition, studies show that by submitting a microorganism to low doses of gamma radiation, stimuli are promoted, which could increase the function, cell resistance, and the growth. Therefore, this study aimed to evaluate the effects of low doses of gamma radiation on the growth and lipid synthesis of Yarrowia lipolytica. The yeast received irradiation doses of: (control); 0.3; 0.5; 0.75; 1.0; 1.25 and 2.5 kGy gamma radiation dose rate in 0.259 kGy/h. Neubauer Chamber was used to analyze cell viability of the yeast. A growth curve and survival curve was determined by spectrophotometry. Then, the yeast was inoculated in the medium composed of syrup sugarcane and vinasse and incubated for 7, 14 and 21 days for the obtaining of dry biomass, by lyophilization, and lipid synthesis, by extraction methodology. The low doses of irradiation had no effect on the growth, survival, and production of dry biomass of Y. lipolytica. For the incubation periods, there was interference in the final production; the highest production was obtained on day 14 (13.46 g/L). The results for lipid synthesis revealed interference with the final production of lipids, being better at a dose of 0.5 kGy to 21 days incubation with yield of 4.17 g/L (34.94%). In conclusion, the low doses of irradiation had no effect on the growth, survival and biomass production of Y. lipolytica. Hormetic effect was observed only in the lipid synthesis, when the radiation dose was associated with the incubation time

Radiation from Computed Tomography (CT) is now the major contributor to population radiation dose. Despite controversy around the dose-effect relationship of radiation from CT, the linear non-threshold (LNT) theory is endorsed by many authorities, and constitutes the basis of cancer risk estimates. The purpose of this study was (1) a literature review of radiobiological theories, and methods of dose saving stategies in CT; (2) to highlight the importance of dose saving in CT, and to demonstrate how dose can be saved in a radiology department: Following a 40% reduction in reference X-ray tube current for a CT of the urinary tract, the effecitve dose and estimated lifetime attributable risk of incident cancer due to this CT in a group (n=103) were reduced by 37% and 38% in an age and sex-matched group respectively. The literature review showed that the public health implications of CT radiation exposure remain uncertain. / Health Studies / M.A. (Public Health)

Radiation from Computed Tomography (CT) is now the major contributor to population radiation dose. Despite controversy around the dose-effect relationship of radiation from CT, the linear non-threshold (LNT) theory is endorsed by many authorities, and constitutes the basis of cancer risk estimates. The purpose of this study was (1) a literature review of radiobiological theories, and methods of dose saving stategies in CT; (2) to highlight the importance of dose saving in CT, and to demonstrate how dose can be saved in a radiology department: Following a 40% reduction in reference X-ray tube current for a CT of the urinary tract, the effecitve dose and estimated lifetime attributable risk of incident cancer due to this CT in a group (n=103) were reduced by 37% and 38% in an age and sex-matched group respectively. The literature review showed that the public health implications of CT radiation exposure remain uncertain. / Health Studies / M.A. (Public Health)