A microdosimetric-kinetic model for the sensitization of v79 cells to radiation by incorporation of bromodeoxyuridine.
Hawkins, R. B. A Microdosimetric-Kinetic Model for the Sensitization of V79 Cells to Radiation by Incorporation of Bromodeoxyuridine. Radiat. Res. 155, 698-702 (2001). The sensitization of G(1)-phase V79 cells to killing by ionizing radiation through incorporation of bromodeoxyuridine (BrdU) in their DNA has been reported to occur exclusively through an increase in the value of the quadratic parameter of the linear-quadratic survival relationship (beta) with no change in the linear parameter (alpha). The consequence of this, as understood through the microdosimetric-kinetic model of cell survival, is discussed. It is shown that the invariance of alpha implies that sensitization is due solely to a decrease in the rate of repair of the initial (potentially lethal) lesions in DNA containing BrdU. Further, for alpha to be unchanged, the average size of the compartments into which the nucleus is partitioned (domains), as postulated in the microdosimetric-kinetic model, must vary in proportion to the reciprocal of the square root of the rate constant for repair of the DNA lesions. This implies that the domain is not a structural subunit of the nucleus. It is a surrogate representation of the consequence of lesions in DNA being restricted to a region in the vicinity of the location in the nucleus at which they are created. A lesion is confined because the distance it can diffuse by random flight to react with another lesion to form a lethal lesion is restricted because a lesion's lifetime is limited by the repair process.
Hawkins
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Department of Radiation Oncology, Alton Ochsner Medical Foundation and Ochsner Clinic, 1514 Jefferson Highway, New Orleans, Louisiana 70121, USA.
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016193:G1 Phase / Q000528:radiation effects; D007700:Kinetics; D011829:Radiation Dosage
D004247:DNA; D001973:Bromodeoxyuridine; D004121:Dimethyl Sulfoxide