The effect of intraspinal cytosine arabinoside on the re-irradiation tolerance of the cervical spinal cord of young and adult rats (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 1989
The effect of intraperitoneal high dose (9 g/kg) Cytosine Arabinoside (Ara-C) on the early delayed radiation response of the rat cervical spinal cord has been studied. When given 2 hrs before irradiation, systemically admhtistered Ara-C significantly reduces the isoeffect doses for the induction of paralysis due to white matter necrosis by a factor of approximately 1.2 for both a single irradiation treatment and for a two fraction irradiation with 24 hr interval. Wo effect on the latency time to develop paralysis was recorded. Cytosine-arabinoside, Spinal cord tolerance, Combined cytosine-arabinoside and irradiation, Radiation dose modification.
Influence of combined use of nicotinamide and carbogen on rat spinal cord radiation tolerance
Radiotherapy and Oncology, 1994
The effect of combining oxygen or carbogen breathing with the systemic administration of nicotinamide (NA) on spinal cord tolerance in Ethrane anesthetised male WAG/Rij rats has been investigated. Ten fraction experiments were carried out with daily (24 h between fractions) and twice a day fractionation (8 h between fractions). Nicotinamide (500 mg/kg) was injected 1 h prior to each irradiation. In addition, a lo-fraction experiment with daily intervals was carried out in which NA was added immediately after irradiation under carbogen breathing conditions. Single dose irradiations showed a minimal decrease in ED, from 21 Gy in oxygen conditions to 19.9 Gy in carbogen conditions and 19.4 Gy when combined with NA. In the fractionation experiments, comparing the response to irradiation in oxygen (0) and nicotinamide oxygen (NO) conditions for the 24-h interval experiment, the EDSo for 0 was 61.6 Gy compared with 54.5 Gy for NO. When carbogen (C) was compared with nicotinamide carbogen (NC), the ED, for C was 62.3 Gy and 53.9 Gy for NC. When NA was administered immediately after irradiation under carbogen breathing conditions the EDso increased to 57.8 Gy. For twice a day fractionation the modifying effect of nicotinamide was similar to that observed for daily fractionation (ED,, of 57.9 Gy for 0, 57 Gy for C and 50.9 Gy for CN), when corrected for incomplete repair in between the two fractions given on 1 day. In conclusion, combining nicotinamide with irradiation while breathing oxygen or carbogen could lead to a reduction of the spinal cord tolerance of approximately 15%, or even 25% when corrected for biological effectiveness based on the LQ formula. This effect should be taken into account in planning clinical studies.
Radiation tolerance and fractionation sensitivity of the developing rat cervical spinal cord
International Journal of Radiation Oncology*Biology*Physics, 1992
To investigate the influence of age at irradiation on single dose radiation tolerance and fractionation sensitivity, the cervical spinal cord of rats was irradiated at the age of 1 week and at 15-18 weeks (adult). While the main histological lesions seem to be comparable after irradiation at the two ages, differences were found in single dose tolerance, latency to paresis due to white matter lesions, and fractionation sensitivity. The 50% effect dose (EDso) for single dose irradiation at one week was 19.5 Gy, which is only lo%, but significantly (p < 0.05), lower than the EDg of about 21.5 Gy at 3 weeks and above. The latency to paresis was clearly influenced by the age at irradiation. The latency in the rats irradiated at 1 week was about 2 weeks, while for adult rats a latency of about 8 months was observed. The fractionation sensitivity for irradiation at 1 week was lower than the fractionation sensitivity of the adult rats; the (Y/B value at 1 week was estimated to be 4.5 Gy, while for the adult rats an (Y/B value of 1.8 Gy was found. As a consequence, the observed small difference in tolerance to single doses between 1 week-old and adult rats is further enhanced after fractionated irradiation. During prolonged irradiation treatments this decreased tolerance may be compensated by a higher proliferation rate in the immature central nervous system. The results of the present experiments indicate that, for a single tissue and endpoint, paresis due to white matter lesions in the rat cervical spinal cord, the latency to expression of damage and the fractionation sensitivity clearly change with age at irradiation.
Late effects of radiation on the lumbar spinal cord of guinea pigs: Re-treatment tolerance
International Journal of Radiation Oncology*Biology*Physics, 1993
Purpose: Using a guinea pig model of lumbar myelopathy, various factors affecting the tolerance of spinal cord to irradiation were assessed: (a) extent of initial injury (b) time interval between priming and test doses (c) animal age at the time of initial radiation treatment. Methods and Materials: A 3 cm section of lumbar spinal cord of guinea pigs was irradiated with fractionated doses of 4.5 Gy gamma rays given as 9 fractions per week. Guinea pigs were primed with 9 X 4.5 Gy in 7 days which is 60% of the EDSo for a continuous course of treatment. After 28 or 40 weeks, animals were retreated with 6-14 fractions of 4.5 Gy. Animals were observed for 2 years following the priming dose and both the incidence and latency of myelopathy recorded. Results: Young adult guinea pigs (8 wk old) showed both a decreased radiation tolerance and latency compared to oldindividuals (40 wk old). At 28 or 40 wk after 9 X 4.5 Gy, only about 8% of the initial injury was remembered in young adult guinea pigs. Conclusion: The amount of residual injury was dependent on the initial damage as a proportion of the tolerance dose. The spinal cord shows a greater capacity for long-term recovery than generally appreciated and re-treatment doses clinically prescribed may be lower than necessary.
International Journal of Radiation Oncology*Biology*Physics, 2006
Purpose: The tolerance of the rat spinal cord to photon and carbon ion irradiations was investigated to determine the relative biologic effectiveness (RBE) of carbon ions ( 12 C) in the plateau region and in a 1 cm spread-out Bragg-peak. Methods and Materials: The cranial part of the cervical and thoracic spinal cord of 336 rats was irradiated with 6 or 18 fractions (Fx) of photons or 12 C-ions, respectively. Animals were followed up for 300 days for the onset of paresis grade II and dose-response curves were calculated. Results: The D 50 -values (dose at 50% complication probability) were 42.9 ؎ 0.5 Gy, 62.2 ؎ 0.9 Gy (6 and 18 Fx, 12 C-plateau) and 19.2 ؎ 0.2 Gy, 17.6 ؎ 0.2 Gy (6 and 18 Fx 12 C-peak), respectively. For photons, the D 50 -values were 57.0 ؎ 0.7 Gy for 6 and 88.6 ؎ 0.7 Gy for 18 Fx. The corresponding RBE-values were 1.33 ؎ 0.02, 1.42 ؎ 0.02 (6 and 18 Fx, 12 C-plateau) and 2.97 ؎ 0.05, 5.04 ؎ 0.08 (6 and 18 Fx 12 C-peak), respectively. Including data of a previously performed experiment for 1 and 2 Fx (1) the parameter ␣/ of the LQ-model was found to be 2.8 ؎ 0.4 Gy, 2.1 ؎ 0.4 Gy and 37.0 ؎ 5.3 Gy for photon-, 12 C-plateau-and 12 C-peak irradiations, respectively. Conclusions: Carbon ion irradiations of the spinal cord are significantly more effective in the peak than in the plateau region. The ␣/-values indicate a significant fractionation effect only for the plateau irradiations. In the Bragg-peak, the applied RBE-model correctly describes the main features although it generally underestimates the RBE by 25%. In the plateau region, maximum deviations of up to 20% were found. The acquired data contribute significantly to the validation of the applied RBE-model. © 2006 Elsevier Inc.