Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder.
Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12-14 week-old C3D2F1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period (p < 10(-8)). The alpha/beta ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly (p = 0.03), but the alpha/beta ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high alpha/beta ratio for this late endpoint.
Bentzen
S M
SM
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Lundbeck
F
F
Christensen
L L
LL
Overgaard
J
J
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015994:Incidence; D016013:Likelihood Functions; D051379:Mice; D008815:Mice, Inbred Strains; D011312:Pressure; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011836:Radiation Tolerance; D013997:Time Factors; D001743:Urinary Bladder / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014563:Urodynamics / Q000528:radiation effects; D014965:X-Rays