[Photodynamic therapy of zinc sulfonated phthalocyanine on murine transplanted tumors, its tissue distribution, and damaging effect on DNA of cancer cell].

Zinc sulfonated phthalocyanine (ZnSPc) 10 mg.kg-1 was injected iv into mice bearing S-180 and RA795 lung carcinoma, after 24 h tumor site were irradiated with red light. In mice bearing S-180, tumor regression rate was 31.8-43.5%, tumor growth inhibition rate was 57.4%. The highest concentration was in tumor tissue 24 h after injection of this dye, on d 5 it still retained relatively highest concentration. However, in most other tissues the dye was not detected at this time, disappearance of ZnSPc from plasma was rapid, it showed an open two compartment model, t1/2 alpha 135.8 min, t1/2 beta 70.1 h, Vd 1.92 x 10(-3) L. In blood, most ZnSPc was bound with plasma protein, the peak light absorption showed blue shift. ZnSPc 2.5 micrograms.ml-1 plus light, percent of DNA double strands greatly decreased, this indicated that DNA was one of target sites for ZnSPc photodynamic action.

[Photodynamic action of hypocrellin A on hepatoma cell mitochondria and microsomes].

Hypocrellin A (HA), a perylene quinone derivative, is a new photosensitizer extracted from Hypocrella bambusae (B et Br) Sace. A high voltage sodium lamp was used as the light source; the illumination intensity was 105 mW/cm2. After HA 25 micrograms/ml and illumination for 10 min, mitochondrial ATPase and microsomal G-6-Pase of hepatoma cells were intensively inhibited, but mitochondrial MAO was not affected. Sulfhydryl contents of the mitochondrial and microsomal membrane proteins were significantly reduced. Lipid peroxidation of mitochondrial and microsomal membrane lipids were greatly enhanced. It is concluded that mitochondria and microsomes are the sensitive targets in cells with respect to HA photosensitization.

[Effect and toxicity of entrapped polysiloxane 5-Fu polycondensate].

Entrapped 5-Fu polysiloxane polycondensate (DMS-Fu) and equivalent doses of 5-Fu were tested on S-180 mice. At the dose of 100 mg/kg, the inhibition potency of these two compounds on tumor was similar, but the inhibition on the body weight was more marked in 5-Fu treated mice. At the dose of 250 mg/kg, all mice treated with 5-Fu died of toxicity but the mice treated with DMS-Fu survived and showed no obvious toxic effect. At the dose of 150-200 mg/kg, the peripheral white blood cells and the bone marrow nucleated cells of 5-Fu treated mice were seriously reduced, which lasted for several days before recovery. In the DMS-Fu group, the inhibition was mild.

[Photodynamic effect of several hematoporphyrin derivatives and their production of singlet oxygen and retention in cancer cells].

Photodynamic effect of three hematoporphyrin derivatives (HpD) on cancer cells in Ehrlich ascites carcinoma (EAC) mice were tested both in vivo and in vitro. At the dose of 5 micrograms/ml, HpD-81 and HpD-83 plus light inhibited the increase of ascites at inhibition rates of 84.6% and 17.5%. Yet HpD-82 plus light showed no effect. Their capacity to retain themselves in cancer cells differed and was related to their photodynamic effect. HpD-81 had the greatest capacity and its distribution ratio was higher than the others. The accumulation of HpD in cancer cells was obviously decreased by the addition of serum in the medium. The production rate of singlet oxygen by HpD-81 was slightly greater than that of HpD-83, but this difference could hardly explain the difference in cytotoxic effect of these two HpD. We expect that the accumulation of HpD in cancer cells may be one of the determinants in the photodynamic effect of photosensitizers.

[Effect of hematoporphyrin derivative (HpD) on nucleoside transport and nucleoside kinase activity of cancer cells].

The HpD and dihematoporphyrin ethers (Photofrin II) at the dose of 5 micrograms/ml significantly inhibited the transport and uptake of thymidine and uridine in Ehrlich ascites carcinoma (EAC) cells. The 50% inhibiting doses (ID50) of HpD and Photofrin II II for thymidine uptake were 1.0 microgram/ml and 7.0 micrograms/ml, and for uridine were 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. The uptake kinetics were greatly changed. The Km values were increased and the Vmax values decreased. The incorporation of 3H-TdR and 3H-UR into the acid-soluble and insoluble materials of EAC cells was depressed. HpD at the dose of 10 micrograms/ml did not influence the activity of thymidine kinase but the uridine kinase activity was mildly inhibited. These results show that the cell membrane may be the initial acting site by both drugs.

[Influencing factors in the leakage of liposome and arabinoside cytosine (ARA-C) entrapped in liposomes in treatment of L1210 mouse leukemia].

Ara-c entrapped into multilamella vesicles (MLV's) composed of PC:C (2:1) (phosphotidylcholine, cholesterol) or PC:SM (1:4) (sphingomyelin) was incubated in the simple salt medium at 37 degrees C for one hour. Its leakage from the liposomes was 5.6-17.6% but, in the presence of serum, the leakage was 35.7-49.1%. Having been incubated at 37 degrees C overnight, the leakage significantly increased but the leakage rate was the highest within the 1st hour. When ara-c entrapped into reverse evaporation vesicles (REV's) composed of PC:C (2:1) or PC:SM (1:4) was incubated in the simple salt medium at 37 degrees C for one hour, its leakage was 2.4-4.1% but, in the presence of serum, the leakage was 10.9-8.2%. When the liposomes were incubated at 37 degrees C overnight, the leakage gradually increased. Whether in the presence of serum or not, the leakage from REV's was much less than that from MLV's. There was no effect on the survival of L1210 leukemia mice when free ara-c was injected intraperitoneally once at the dose of 10 mg/kg, but when the same dose was given for five times, the increase rate in life span was 43.2--51.3%. When ara-c, entrapped into MLV's or REV's composed of PC:C (2:1) and PC:SM (1:4), was given at the dose of 10 mg/kg only once, the effect of intraperitoneal injection was more marked than that of intravenous injection. No effect was observed when free ara-c was continuously infused at the dose of 2 mg/kg once everyday for five days.(ABSTRACT TRUNCATED AT 250 WORDS)

Photosensitization of mitochondrial adenosine-triphosphatase and adenylate kinase by hematoporphyrin derivative in vitro.

Mitochondrial ATPase and adenylate kinase activity of hepatoma cells were inhibited by hematoporphyrin derivative (HPD) followed by photoirradiation. Inhibition of ATPase activity was a dose- and time-related event. Malonaldehyde (MDA) content of mitochondrial membranes was markedly increased by HPD plus light. The content of mouse liver microsomal cytochrome P-450 was greatly increased after intraperitoneal injection of HPD for 4 days (5 mg/kg/day). The liver weight, and levels of liver microsomal G-6-phosphatase, MDA and triglyceride (TG) showed no difference in treated vs. control animals. The data presented here demonstrate that mitochondria may be a sensitive site of action of HPD photosensitization, and inactivation of ATPase and adenylate kinase may be an important contributing factor to tumor cell damage and death.