ABSTRACT
BACKGROUND: The growth kinetics of tumors after irradiation (Figure 1) is defined by cells surviving with delayed reproductive death (DRD). The prediction of radiation sensitivity of locally recurrent tumor growth is among other factors dependent on the knowledge of the impact of fractionated irradiation on these surviving cells with DRD. Short recovery effects can be estimated in vitro by comparing the difference of the medians of the distributions of clone sizes, the median clone sizes difference (MCD) after single and split exposure irradiation of the progenitor cells. MATERIALS AND METHODS: CHO-cells of a sub clone of the line T71 have a spontaneous cell loss rate of < 5%. The cells were irradiated a) by a single exposure 3 hours after synchronization and b) by a fractionated irradiation of half the exposure of a 200-kVp radiation exposure 3 hours and 6 hours after synchronization, respectively. Clone survival was determined (Figure 2). As function of dose and incubation time the distributions of clone sizes and the MCD were determined by tapping the clone cells in microscopic projections. RESULTS: The radiation sensitivity El of the DRD can be defined as the proportional factor of the linear relationship between the MCD on one side and the dose K x the cell division factor m on the other side. EI is dependent on the age of the cells during irradiation (Figure 3) and the cell line (Table 1). The slope of the dually logarithmic growth curve of the cell population is: s = 1 - El.K. Experimentally El was found to be equal for single and split dose irradiation (Figures 4 and 5) and amounted to El = 0.065 with Sd = +/- 0.004.--Literature analysis for the mathematical estimation of El.K (Figure 6) was based on reports of measurements of the local tumor recurrence growth of carcinomas and sarcomas of rodents and pulmonary metastases of sarcomas in humans, respectively, after fractional irradiation. We obtained values of 0 < or = El.K < or = 0.77 (Table 2). Values for El are independent of the dose and lie considerably below data derived from in-vitro measurements of different cell cultures. CONCLUSIONS: Since recurrence kinetics of tumors are determined by the radiation sensitivity El of the DRD, El can be used for estimating the kinetics of tumor recurrence. As lately described, MCD is linearly proportional to the micro-nucleus frequency [12]. Determinations of the micro-nucleus frequencies in tumor cell biopsies pre and post radiation onset offer the option for developing a fast predictive assay. Organ malformations of embryos after exposition to ionizing radiation can be mathematically deduced by DRD to the partial cell mortality.
