[The mode of action of bleomycin-cell kinetic investigations (author's transl)]

Abstract

Chemotherapy of malignant ENT tumours with Bleomycin (BLM) alone is not very successful. In the last time however several authors pointed out much better therapeutic results when BLM therapy has been combined with radiation treatment It is farly unknown why this combination should cause a greater therapeutic effect. Therefore we investigated the following questions: 1. In what manner does BLM influence the kinetics of cell proliferation of malignant tissues? 2. Does BLM synchronize the tumour cells or is the greater therapeutic success of a combination of BLM and X rays only depending an an additional effect? 3. Can we find a connection between the effect of BLM and the histology of the tumour? With cell kinetic methods (authoradiography, cytophotometry, mitotic index) and histological technics we examined these problems in 5 human ENT tumours and got the following results: 1. BLM initially causes a partial synchronization of the tumour cells (blockade in the S-phase). During a continuous therapy with BLM however the tumour cells will be collected in the late S- and mainly in the G2-phase. But this peak of cells in G2 is not the expression of synchronization because a lot of these cells are blocked irreversible and will leave the cell cycle (hyperceratotic cells). Ffrom those cells which thereupon have entered the mitotic phase a further part of them will by endomitosis or endoreduplication. Only a small group of the cells originally collected in the G2-phase will devide and enter the G1-phase again. Furthermore we observed a distinct recruitment of G0-cells back into the cell cycle (for details see fig. 9). 2. The greater effect of radiation therapy following the application of BLM is not the result of synchronization but of an additional destruction of premitotic G2-cells which properly would have undergone mitosis. BLM and X rays therefore act additionally. 3. The greater therapeutic success of the combination of BLM and radiation treatment comes true only in keratinizing squamous cell carcinoma. The reason is that BLM destroys the tumour cells by hyperkeratosis and polyploidy. Thus BLM must be ineffective in carcinoma without the ability of keratinizing.