Repopulation kinetics in irradiated mouse lip mucosa: the relative importance of treatment protraction and time distribution of irradiations.

The repopulation kinetics of the irradiated lip mucosa of mice has been investigated. Split-dose experiments showed that, in this tissue, repopulation starts within 3 days after the first irradiation and increases exponentially within 10 days. To assess the relative importance of protraction and distribution of irradiations as a function of time, 10 fractions were given in (1) 3 days (three irradiations per day with a 4-hr interval), (2) 11 days (daily fractions), or (3) two short courses, each consisting of five fractions given in 1.5 days separated by a rest period of 8 days, with an overall time of 11 days. The results show that by protracting the treatment from 3 to 11 days (with daily irradiations) repopulation accounts for recovery of approximately 13 Gy. Delivering the radiation in two short courses separated by a rest period leads to an additional recovery of approximately 5 Gy. The most plausible explanation for this observation is that repopulation is much more efficient during the rest period between the two courses than during continuous daily irradiation. Although the regimen of two short courses with a rest period spares the acute reaction, it will not enhance the late tolerance. Before thorough knowledge about the repopulation kinetics of the tumors can be gained, caution should be observed for indiscriminate use of split-course multiple-fraction-per-day (MFD) regimens for treating various tumors.