Date of Award
Doctor of Philosophy
A. F. McFee
J. Grant Brewen, D. O. Richardson, Liane B. Russell, Robert R. Shrode
The rate of induction of chromosome aberrations in pig lymphocytes following 100, 200, JOO and 400 rads of fission neutrons administered in vivo and in vitro was determined. The data from each exposure method were tested for goodness of fit of linear and quadratic models. Numbers of acentric fragments, numbers of rings plus numbers of dicentrics, and the sum of the frequencies of aberration types were well explained by a linear model of the form Y = a + bD + e, where D = dose, a = Y-intercept, b = slope and e = random deviation from the least-squares fitted regres-sion. A statistical comparison between exposure methods, using doses mea-sured in air, indicated a significantly (P < .01) higher aberration index was found following an in vitro exposure of the animal’s blood than was produced by exposing the entire animal. Equations were developed which permitted the prediction of in vivo damage from the in vitro aberration coefficient. Dose attenuation and differences in the relative contribution of the neutron and gamma components reaching the target cells were recognized as factors influencing the biologically effective dose received from the two exposure methods. The average body dose was calculated from measurements made across the width of a tissue-equivalent phantom. From these calculations, it was determined that approximately 56% of the dose measured in air at the animal’s midline was actually received by the blood cells in vivo. When the in vitro aberration data were corrected to the average body dose, aberrations were still present in greater numbers fol-lowing in vitro than in vivo irradiation. The possibility that in vivo mechanisms exist for the preferential removal of damaged lymphocytes was proposed as a plausible explanation for this observation. When the neutron-to-gamma ratios for the two exposure conditions and the relative biological effectiveness of the neutron component were con-sidered, the level of acentric fragments was comparable between exposure methods. Rings plus dicentrics were, however, still more abundant follow-ing in vitro exposures, suggesting that an inherent difference exists between in vivo and in vitro irradiation in rate of induction and repair or that heavily damaged cells are more rapidly removed from the peripheral system. These data cast some doubt also on the validity of assuming that comparable chromosomal damage will be found following in vivo and in vitro irradiation. By sampling peripheral blood at various postexposure intervals, the response of the aberration level as a function of time was studied. A rapid decrease in the proportion of cells containing aberrations was noted as early as 24 hours postexposure. This initial loss coincided with a decrease in lymphocyte number and continued until the recovery of lymphocyte numbers began at 2 days following irradiation. Subsequent losses were less dramatic, and numbers of acentric fragments reached pre-irradiation levels in the lower-dose groups by 56 days post-exposure numbers of rings plus dicentrics persisted throughout the duration of the study. Statistical analyses of the data demonstrated the variability of the aberration coefficient with time postirradiation. Mathematical models are presented which describe the predicted yield of numbers of aberrations as a function of time after irradiation. The hematological data are examined for their possible relation to postirradiation aberration levels. The fate of aberrant lymphocytes fol-lowing irradiation is discussed in relation to the kinetics of the reticuloendothelial system. Selective removal of damaged cells from the peripheral system is suggested. It is concluded that different aberration coefficients will be found in blood sampled from pigs at different postexposure intervals. The kinetics of aberration persistence should therefore be considered when lymphocyte aberrations are employed as biological dosimeters.
Mailhes, John B., "Chromosome aberration persistence and in vivo-in vitro dose responses in pig leukocytes following exposure to fission neutrons. " PhD diss., University of Tennessee, 1972.