Lack of accurate data for epidemiological studies of low dose radiation effects necessitates development of dosimetric models allowing prediction of cancer risks for different organs. The objective of this work is to develop a model of the radiation response of human bronchiolar tissue with single cell resolution. The computer model describes epithelial tissue as an ensemble of individual cells, with the geometry of a human bronchiole and the properties of different cell types are taken into account. The model simulates the tissue kinetics and radiation exposure in four dimensions: three spatial dimensions and a temporal dimension. The bronchiole is modeled as a regular hollow cylinder with the epithelial cells of three different types (basal, secretory, and ciliated) lining its interior. For the purposes of assessment of radiation damage to the cells only the nuclei of the cells have been modeled. Subroutines describing cellular kinetics have been developed to simulate cell turnover in a normal epithelial tissue. Monte Carlo subroutines have been developed to simulate exposure to alpha particles; the GEANT4 toolkit has been used to simulate exposure to low LET radiation. Each hit cell is provided with a record of energy deposition, and this record is passed to the progeny if the cell survives. The model output provides data on the number of basal progenitor cells in different phases of a cell life-cycle and secretory to ciliated cell ratio after several generations of cell proliferation. The model calculates labeling and mitotic indices and estimates the average cell turnover time for the bronchiolar tissue. Microdosimetric calculations are performed for cells traversed by ionizing particles. The model will be used to assess the accumulation of damage in cells due to protracted low level radiation exposure. The model output may provide directions for the future experimental design.

O principal objetivo deste trabalho é fornecer um modelo biocinético validado em termos fisiológicos para a avaliação das doses radiométricas devido à ingestão de [4-14C]-colesterol em humanos. Com o intuito de validar o modelo biocinético proposto para o [4-14C]-Colesterol, os valores de excreção fecal e absorção preditos pelo modelo foram comparados com dados experimentais da literatura, foi obtido um alto grau de concordância entre os resultados de acordo com teste ANOVA (p = 0,416 para os valores de excreção e p = 0,423 para os valores de absorção). Foram calculados os coeficientes de Dose Efetiva (SvBq-1), Dose Equivalente (SvBq-1) e Dose Absorvida (GyBq-1) nos orgãos e tecidos para humanos utilizando a metodologia MIRD e o software de análise compartimental ANACOMP para quatro objetos simuladores que representam: um adulto com massa de 73,3 kg, um adolescente de 15 anos (56,9 kg), uma criança de 10 anos (33,2 kg) e uma criança de cinco anos (19,8 kg). O órgão que obteve a maior Dose Absorvida, para todos os objetos simuladores, foi o intestino grosso inferior (IGI). O conceito da alometria foi utilizado para interpolar o Coeficiente de Dose Absorvida no intestino grosso inferior (DIGI) para massas corpóreas (m) desconhecidas: DIGI(SvBq-1)=161,26.m(kg)-1,025. Para uma mesma quantidade administrada de colesterol, o Coeficiente de Dose Efetiva (E) diminui com o aumento da massa corporal do objeto simulador, em outras palavras, para a mesma atividade administrada os indivíduos com menor massa são submetidos a Doses Efetivas mais elevadas. O conceito de alometria também foi utilizado para interpolar o Coeficiente de Dose Efetiva (E) para massas corpóreas (m) desconhecidas: E(SvBq-1)= 171,1.m(kg)-1,021. / The main objective of this work is to provide a biokinetic model in order to estimate the radiometric dose due to intake of [4-14C]-cholesterol. The model was validated comparing the values of fecal excretion and absorption described in literature with that predicted by the model. The proposed model achieved good concordance between the results (p = 0.416 for excretion and p = 0.423 for absorption). The coefficients of Effective Dose (SvBq-1), Equivalent Dose (SvBq-1) and Absorbed Dose (GyBq-1) in human organs and tissues were calculated using the MIRD methodology and the compartimental analysis software ANACOMP. The coefficients were estimated for four phantoms: (i) adult with a body mass of 73.3 kg, (ii) 15 years old adolescent (56.9 kg), (iii) 10 years old child (33.2 kg) and (iv) five years old child (19.8 kg). The organ that received the highest Absorbed Dose for all phantoms was the lower large intestine (LLI). The allometry theory was used to interpolate the coefficient of absorbed dose in the lower large intestine (DLLI) for unknown body mass (m): DLLI (GyBq-1)=161.26 m (kg)-1.025. For the same administered activity, the Effective Dose Coefficient (E) decreases as the body mass increases. On other words, for the same intake activity, individuals with low body mass are exposed to higher doses. The allometry theory was used to interpolate the coefficient Effective Dose (E) for unknown body mass (m): E(SvB-1)= 171.1 m(kg)-1,021.

O principal objetivo deste trabalho é fornecer um modelo biocinético validado em termos fisiológicos para a avaliação das doses radiométricas devido à ingestão de [4-14C]-colesterol em humanos. Com o intuito de validar o modelo biocinético proposto para o [4-14C]-Colesterol, os valores de excreção fecal e absorção preditos pelo modelo foram comparados com dados experimentais da literatura, foi obtido um alto grau de concordância entre os resultados de acordo com teste ANOVA (p = 0,416 para os valores de excreção e p = 0,423 para os valores de absorção). Foram calculados os coeficientes de Dose Efetiva (SvBq-1), Dose Equivalente (SvBq-1) e Dose Absorvida (GyBq-1) nos orgãos e tecidos para humanos utilizando a metodologia MIRD e o software de análise compartimental ANACOMP para quatro objetos simuladores que representam: um adulto com massa de 73,3 kg, um adolescente de 15 anos (56,9 kg), uma criança de 10 anos (33,2 kg) e uma criança de cinco anos (19,8 kg). O órgão que obteve a maior Dose Absorvida, para todos os objetos simuladores, foi o intestino grosso inferior (IGI). O conceito da alometria foi utilizado para interpolar o Coeficiente de Dose Absorvida no intestino grosso inferior (DIGI) para massas corpóreas (m) desconhecidas: DIGI(SvBq-1)=161,26.m(kg)-1,025. Para uma mesma quantidade administrada de colesterol, o Coeficiente de Dose Efetiva (E) diminui com o aumento da massa corporal do objeto simulador, em outras palavras, para a mesma atividade administrada os indivíduos com menor massa são submetidos a Doses Efetivas mais elevadas. O conceito de alometria também foi utilizado para interpolar o Coeficiente de Dose Efetiva (E) para massas corpóreas (m) desconhecidas: E(SvBq-1)= 171,1.m(kg)-1,021. / The main objective of this work is to provide a biokinetic model in order to estimate the radiometric dose due to intake of [4-14C]-cholesterol. The model was validated comparing the values of fecal excretion and absorption described in literature with that predicted by the model. The proposed model achieved good concordance between the results (p = 0.416 for excretion and p = 0.423 for absorption). The coefficients of Effective Dose (SvBq-1), Equivalent Dose (SvBq-1) and Absorbed Dose (GyBq-1) in human organs and tissues were calculated using the MIRD methodology and the compartimental analysis software ANACOMP. The coefficients were estimated for four phantoms: (i) adult with a body mass of 73.3 kg, (ii) 15 years old adolescent (56.9 kg), (iii) 10 years old child (33.2 kg) and (iv) five years old child (19.8 kg). The organ that received the highest Absorbed Dose for all phantoms was the lower large intestine (LLI). The allometry theory was used to interpolate the coefficient of absorbed dose in the lower large intestine (DLLI) for unknown body mass (m): DLLI (GyBq-1)=161.26 m (kg)-1.025. For the same administered activity, the Effective Dose Coefficient (E) decreases as the body mass increases. On other words, for the same intake activity, individuals with low body mass are exposed to higher doses. The allometry theory was used to interpolate the coefficient Effective Dose (E) for unknown body mass (m): E(SvB-1)= 171.1 m(kg)-1,021.