Radiation Treatment of Human Tumours Following the in Vivo Synchronization of the Cell Cycle

Abstract

During its life the cell passes through a number of developmental stages, an event that is referred to as the cell cycle. In the S-phase of the cycle the DNA is duplicated. All cells of a tissue are statistically distributed over the entire cell cycle and enter into the M-phase at different times, so that we get the impression of a continuous growth of the tissue.

5-fluor-uracil (FU) inhibits DNA-synthesis reversibly, so that the cells accumulate at the beginning of the S-phase. Because of the rapid catabolism of FU the cells pass together through the cell cycle after the blockage is terminated; they will be synchronized.

X-ray beams harm the cells severely in the G₂-phase. Thus a synchronized population should be injured very badly by irradiation in this phase.

With our in vivo and in vitro method we were able to demonstrate that the ³H-index of different tissues taken from 40 patients usually increased about 7 hours after FU infusion and was followed by a peak of mitotic cells 2 hours later as a proof of the synchronized population.

To test whether radiotherapy following synchronization would be successful, we used mice with a carcinoma of the skin induced by benzpyrene. The in this way treated animals showed clearly the lowest tumor growth with a prolongation of life-time compared with the other groups (controls, FU-treated, radiated and combined treated mice).

Working on the results of the animal experiments we used the synchronization method followed by radiotherapy for the treatment of carcinoma-patients who were in definitely incurable condition. In nearly all cases the treatment could be considered beneficial. Serious side effects have not been observed.