Leg contracture in mice: an assay of normal tissue response

Leg contracture, defined as the difference in extensibility of the control and irradiated hind legs of mice, was found to correlate with single doses of radiation from about 20 to 80 Gy. The time of development of the early phase of the response coincided with that reported for the appearance of the acute skin response, and in some cases, partially reversed as this reaction healed. The contracture then progressed again at a moderate rate through 90 days, and then more slowly through one year. Skin contraction, measured by decrease in intertattoo distance, was assayed in the same mice. It followed the same time course as leg contracture, but had a different dose-response relationship. Maximal contraction occurred following doses of 30 Gy or more, reaching this level sooner following higher doses. The early reactions in individual mice were not reliable in predicting late response for either assay. To determine the contribution of skin contraction to the overall leg contracture response, mice were sacrificed and the leg contracture measured before and after the removal of the skin of the leg. After doses of up to 30 Gy, little contracture remained from skinning the leg, indicating that skin contraction was largely responsible for leg contracture in this dose range. After doses of about 45 Gy and above, some contracture remained in the skinned legs, although less than in intact legs. This indicated that injury to the deeper tissues of the leg as well as to the skin was responsible for contracture at these higher doses. There was little or no enhancement of either skin contraction or leg contracture by the hypoxic cell sensitizers metronidazole or misonidazole.