Authors: W F Heidenreich W A Müller H G Paretzke M Rosemann
Publish Date: 2005/04/27
Volume: 44, Issue: 1, Pages: 61-67
Abstract
This paper analyzes data for the osteosarcoma incidence in lifetime experiments of 224Ra injected mice with respect to the importance of initiating and promoting action of ionizing high LETradiation This was done with the biologically motivated two step clonal expansion TSCE model of tumor induction Experimentally derived osteosarcoma incidence in 1194 mice following exposure to 224Ra with different total radiation doses and different fractionation patterns were analyzed together with incidence data from 1710 unirradiated control animals Effects of radiation on the initiating event and on the clonal expansion rate ie on promotion were found to be necessary to explain the observed patterns with this model The data show a distinct inverse protraction effect at high doses whereas at lower doses this effect becomes insignificant Such a behavior is well reproduced in the proposed model At dose rates above 6 mGy/day a longer exposure produces higher ERR per dose while for lower rates the reverse is the case The TSCE model permits the deduction of several kinetic parameters of a postulated twostep bone tumorigenesis process Mean exposure rates of 013 mGy/day are found to double the baseline initiation rate At rates above 100 mGy/day the initiation rate decreases The clonal expansion rate is doubled at 8 mGy/day and it levels out at rates beyond 100 mGy/day
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