RELATIONSHIP BETWEEN PHOTODYNAMICALLY INDUCED DAMAGE TO VARIOUS CELLULAR-PARAMETERS AND LOSS OF CLONOGENICITY IN DIFFERENT CELL-TYPES WITH HEMATOPORPHYRIN DERIVATIVE AS SENSITIZER
Lc. Penning et al., RELATIONSHIP BETWEEN PHOTODYNAMICALLY INDUCED DAMAGE TO VARIOUS CELLULAR-PARAMETERS AND LOSS OF CLONOGENICITY IN DIFFERENT CELL-TYPES WITH HEMATOPORPHYRIN DERIVATIVE AS SENSITIZER, Biochimica et biophysica acta. Molecular cell research, 1221(3), 1994, pp. 250-258
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.