RELATIONSHIP BETWEEN PHOTODYNAMICALLY INDUCED DAMAGE TO VARIOUS CELLULAR-PARAMETERS AND LOSS OF CLONOGENICITY IN DIFFERENT CELL-TYPES WITH HEMATOPORPHYRIN DERIVATIVE AS SENSITIZER

The possible causal relationship between various forms of photodynamic ally inflicted damage and reproductive cell death of cultivated cells was evaluated according to three criteria. The probability for the exi stence of such a relationship is high, when the particular form of cel lular damage (i) exhibits a dose-effect curve, comparable to the dose- effect curve of loss of clonogenicity, (ii) is not readily repairable during further incubation of the treated cells and (iii) varies in a w ay comparable to the loss of clonogenicity under varying experimental conditions. According to these criteria it could be shown that many fo rms of photodynamically inflicted cellular damage are presumably not d irectly involved in loss of clonogenicity. Only for a few kinds of cel lular damage studied in the present investigations was the probability for a causal relationship with reproductive cell death much higher. F or L929 fibroblasts this is either an inhibition of the Na+/K+-ATPase activity, or a relatively slight DNA damage combined with a strong inh ibition of DNA excision repair. For T24 human bladder carcinoma cells the kinds of cellular damage that may be causally related to reproduct ive cell death are again inhibition of Na+/K+-ATPase activity, inhibit ion of amino-acid (AIB and glycine) transport activity or impairment o f mitochondrial function. Finally, for CHO cells, inhibition of leucin e and phenylalanine transport and impairment of mitochondrial function may be crucial for loss of clonogenicity. These results indicate that the pathways leading to photodynamically induced reproductive cell de ath may be quite different for different cell types.