Upper dose thresholds for radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, radiation-sensitive Trp53 heterozygous mice.
Trp53 heterozygous mice are radiation-sensitive and cancer-prone. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co gamma radiation at high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received 10 or 100 mGy at low dose rate 24 h prior to the 4-Gy dose. Tumor frequency and latency were measured over the animals' life span. Exposure to 10 mGy prior to 4 Gy resulted in a small (approximately 5%) but significant life-span regain and increased latency (approximately 9%) for all malignant tumors taken together, but 100 mGy further reduced life span slightly (approximately 7%). Latency responses were tumor type-specific. The prior 10-mGy exposure resulted in a small (approximately 7%) regain in latency for lymphomas but no change in latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the increase in lymphoma latency and further reduced life span (approximately 8%). A 10-mGy dose prior to 4 Gy at low dose rate had no effects. Adapting exposures had no significant effect on tumor frequency. We conclude that a single low dose induced a small protective response in vivo in Trp53+/- mice, reducing the carcinogenic effects of a subsequent large, high-dose-rate exposure by increasing tumor latency. The upper dose threshold at which low-dose protective effects gave way to detrimental effects was tumor type-specific, as found previously for spontaneous tumors in these same cancer-prone mice (Radiat. Res. 159, 320-327, 2003). However, the upper dose thresholds appear to be lower (below 100 mGy) for radiation-induced tumors than for the same tumors appearing spontaneously.
Mitchel
R E J
RE
Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, Ontario, K0J 1J0 Canada. mitchelr@aecl.ca
Jackson
J S
JS
Carlisle
S M
SM
D000222:Adaptation, Physiological; D000818:Animals; D001859:Bone Neoplasms / Q000209:etiology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016158:Genes, p53 / Q000502:physiology*; D006579:Heterozygote; D008223:Lymphoma / Q000209:etiology; D008297:Male; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D012516:Osteosarcoma / Q000209:etiology; D011836:Radiation Tolerance