Different immobilization procedures during irradiation influence the estimation of alpha/beta ratios in mouse lip mucosa

Abstract

In previous experiments an anaesthetic gas mixture of enflurane (Ethrane, Abbott, Belgium) and oxygen has been used in our department to position mice for local irradiation. The development of a new immobilization method allowed the investigation of possible dose modifying effects of enflurane with different gases as carrier on the radiation response of mouse lip mucosa. The effect of different immobilization procedures on single dose and fractionated irradiations was examined. The experiments were compared on the basis of the dose associated with 50% incidence of lower lip desquamation (ED50 +/- 95% CI). When mice were breathing air the ED50 value following single dose irradiation was 20.0 (19.6 to 20.5) Gy. For mice receiving an anaesthetic gas mixture of enflurane and oxygen the ED50 was decreased significantly to 17.5 (17.2 to 17.8) Gy, indicating a sensitizing effect of the anaesthetic mixture by a factor of 1.14. The impact of different experimental set-ups on the fractionation sensitivity has been assessed. In order to estimate alpha/beta ratios in different treatment conditions two and ten fraction experiments were performed, additionally to the single dose irradiations. Dose modification factors were 1.09 for two fractions and 0.97 for the ten fraction experiment. This varying dose modification leads to a pronounced shift in alpha/beta ratios (estimated by "direct analysis" and graphically illustrated with a Fe-plot). For air breathing animals an alpha/beta ratio of 16.4 (14.5 to 18.9) Gy was estimated by direct analysis, whereas for the enflurane/oxygen anaesthesia 8.7 (7.3 to 10.2) Gy were calculated. Both these data sets were adequately described with the linear-quadratic formalism, as was shown with Tucker's analysis. The sensitizing effect of oxygen alone in single dose irradiations (DMF: 1.07) suggests moderate physiological hypoxia in mouse lip mucosa. The present data emphasize the effect of different immobilization procedures on the estimation of alpha/beta ratios, especially when large fraction sizes are involved. Data from experiments involving large fraction sizes should be avoided in the estimation of repair parameters. Further experimental work has to be carried out to elucidate the possible dose modifying effects of anaesthetic agents in clinical practice, e.g. for infants and for patients undergoing intraoperative radiotherapy.