The incorporation of thymidine, uridine and leucine into DNA, RNA and proteins, respectively, was measured in log‐phase Chinese hamster cells photosensitized by chloroaluminum phthalo‐cyanine tetrasulfonate (A1PCS). Post‐treatment synthesis of all macromolecules was inhibited. The inhibition became progressively more pronounced with time, reaching a maximum at ca. 3 h after treatment. The differences between relative sensitivity of protein, RNA and DNA syntheses to A1PCS photosensitization, were not statistically significant. Some of the observed inhibition was due to a reduced uptake of the labeled precursors from the growth medium. Energy metabolism, as reflected by glucose oxidation, was sensitive to A1PCS plus light. Inhibition of glucose oxidation was evident immediately after treatment, and became more pronounced with time. Following a sublethal light fluence, maximum inhibition was observed at 3 h and there was a gradual recovery at later times. Inhibition of glucose oxidation was about two fold higher in plateau‐phase compared to log‐phase cells. The former were also twice as sensitive with respect to cell killing. These results suggest that inhibition of glucose oxidation induced by mitochondrial damage as seen in human lymphocytes, may be a primary cause for AlPCS‐photosensitized cell killing.

The aim of the present study was to examine calcium metabolism of the renal cortex in experimental chronic renal failure, together with morphologic criteria of nephrocalcinosis and to determine the effect of chronic verapamil administration on these parameters. In subtotally nephrectomized (SNX) rats 3 weeks after surgery, renal cortical calcium content increased more than two-fold. 45Ca incorporation into renal cortical slices in SNX revealed a 35% increase, associated with a 50% increase in a lanthanum-resistant fraction of 45Ca uptake. Radiocalcium wash-out curves in this group demonstrated abnormal retention of the isotope for up to 30 min of incubation. In contrast, radiocalcium incorporation and wash-out in SNX rats chronically treated with verapamil were similar to that obtained in the sham group. Verapamil administration significantly reduced, but did not normalize, renal cortical calcium content. Von Kossa staining demonstrated the deposition of calcium in the renal parenchyma of SNX rats. Ultrastructurally, it was accompanied by mitochondrial disorganization and calcification, as well as by the tubular basement membrane destruction and mineralization. These morphologic patterns of nephrocalcinosis were significantly ameliorated in SNX rats treated with verapamil. We conclude that chronic verapamil administration results in amelioration of uremic nephrocalcinosis.

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Recent studies point to the naturally occurring molecules in expression of radiation damage and in protection. DNA repair was shown to be one of the parameters that can be modified to attain improved protection. The need for a natural compound that can enhance DNA repair in order to improve cellular protection focused our attention on nicotinamide (NA). The effects of addition of NA, a precursor for NAD+ synthesis, on the DNA repair capacity following gamma and ultraviolet irradiations were studied in several repair-proficient and repair-deficient cell lines. The addition of low concentrations of NA (less than 3 mM) resulted in increased repair synthesis in the repair-proficient cells. Addition to repair-deficient cells resulted in decreased repair synthesis. Cells which repair damage from one type of radiation, and not from another, responded accordingly to the presence of NA. However, addition of high concentrations of NA to repair-proficient cells resulted in decreased repair synthesis. Thus, nicotinamide can improve the repair capacity in a concentration-dependent manner, but it clearly requires the existence of functional repair processes.

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0.165 to 3.3 kJ m-2 min-1 was studied in Chinese hamster cells and human lymphocytes, using as endpoints colony-forming ability and inhibition of [3H]thymidine incorporation following mitogenic stimulation and dye-photoactivation, respectively. Using Chinese hamster cells exposed to photoexcited chloroaluminium phthalocyanine tetrasulphonate in PBS solution, cytotoxicity was diminished as the fluence rate was reduced. In human lymphocytes changing the fluence rate between 0.33 and 3.3 kJ m-2 min-1 affected the response in a way similar to that of Chinese hamster cells. Human lymphocytes, when exposed to incremental increasing light fluences, 4 h after a conditioning dose, were able to recover from phthalocyanine-induced photodamage, as evidenced by the reappearance of a shoulder on the dose-effect curve. This recovery process during a protracted light exposure, could explain the reduced sensitivity to phthalocyanine photosensitization, compared to exposure at high fluence rates.