Cellular Radiobiology Chapter 32 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Target Theory DNA is the target molecule Cell death only occurs if target molecule is inactivated Hits can be indirect or direct 2 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

HITS LOW LET & OER = low Probability of target hits O2 presence = free radicals And increased volume leading To an increased hit probability High LET = close ionizations And an increase hit probability O2 presence = no extra hits; Max # hits there with direct and high LET 3 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Cell-Survival Kinetics Single-Target, Single-Hit Model: biological targets (bacteria) Multitarget, Single-Hit Model: human cells -dose threshold Random rain drops and ratio of wet to dry squares. Increased # or drops = decreased # of dry squares After irradiation of 1000 cells, the dose-response is exponential D37 is the dose that results in 37% survival. 4 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Cell-Survival Kinetics cont. Low D37 = High radiosensitivity (more surviving cells) Split squares require both halves to be hit for square to be wet Multitarget, single hit model of cell survival is characteristic of human cells Do is mean lethal dose; Dq is threshold dose 5 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Recovery Some damage must be accumulated before the cell dies; this is called sublethal damage The wider the shoulder of the graph the more sublethal damage For full recovery the time between each split cell dose must be at least as long as the cell generation time, usually 24 hrs G1 is the most time variable of the cell phases Human cells are most radiosensative in M phase and most radioresistant in late S See next two slides for pictures 6 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Split-dose Irradiation 7 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

Cell-Cycle Effects 8 Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved.

RBE and OER O2 presence maximizes the effect of low-LET radiation High-LET show little difference with O2 presence RBE and OER Copyright © 2013 by Mosby, Inc., an affiliate of Elsevier Inc. All rights reserved. 9

THE END Exam Next week 9:30 – 11 AM HSH for Second Group 8-9:30 Faculty going to ACERT PM