Effects of continuous low-dose-rate brachytherapy on the rectum of the rat.

The dose-limiting factor in essentially all curative radiotherapy is damage to normal tissue. In spite of this, our understanding of radiation-induced damage to normal tissue leaves much to be desired. Damage to the rectum is often observed after clinical brachytherapy of pelvic malignancies. A model in which the rectum of the rat is irradiated with a uniform and reproducible dose of brachytherapy irradiation was developed. This system consists of an intracavitary applicator, which is used in conjunction with methods that reduce fecal flow, a jacket that restrains rat movement and a lead-shielded chamber to contain rats during low-dose-rate brachytherapy. Irradiation was applied in 48-h intervals separated by 48-h breaks during which the applicator was removed. Methods to analyze the sequelae of brachytherapy irradiation of the rectum were also developed. The total dose of 0.75 Gy/h continuous low-dose-rate brachytherapy required to produce obstruction in the rat rectum has been measured. The ED50 was 70.6 +/- 4.2 Gy. The length of time between irradiation and obstruction was also correlated with total dose. Other effects on the rectum that were related to dose were diarrhea and rectovaginal fistula. This irradiation system can produce uniform and reliable brachytherapy doses to the rat rectum. The late effects in normal tissues observed in this model are similar to those observed in humans after irradiation of the rectum. The model should be appropriate for analyzing relative changes in the rectum resulting from different dose rates and fractionation schemes relevant to brachytherapy.