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At least 937 records · Page 52Linked to original sources
PubMed1985

Cellular pharmacology in murine and human leukemic cell lines of diaziquone (NSC 182986).

We investigated the in vitro interaction with and antitumor effect on several murine and human leukemic cell lines of diaziquone (AZQ). L1210 cells accumulated AZQ from Roswell Park Memorial Institute Medium 1640 with or without newborn calf serum by a temperature-dependent and sodium azide-resistant process. AZQ inhibited, in a dose-dependent fashion, [3H]thymidine incorporation into L1210 cells, but this inhibition was slow to develop, requiring approximately 6 hr to become apparent. The minimal inhibitory concentration of AZQ for this process was 0.05 to 0.25 nmol/ml. AZQ was a much less effective inhibitor of L1210 cell [3H]uridine and [14C]valine incorporation. In suspension cultures, AZQ inhibited growth of L1210 and HL-60 cells at minimal inhibitory concentrations of 0.5 to 1 nmol/ml. In soft agar cultures, AZQ inhibited HL-60 cell cloning at minimal inhibitory concentrations of 0.1 to 0.3 nmol/ml. AZQ provoked a dose-dependent increase in oxygen consumption when added to intact L1210, HL-60, and K562 cells and was converted to an AZQ anion free radical by these cells. When the aziridine rings of AZQ were opened by acid treatment, the resulting molecule was not accumulated by L1210 cells, did not provoke O2 consumption, did not form free radicals when added to L1210 cells, and was a much less effective inhibitor of [3H]thymidine incorporation by L1210 cells than was AZQ.

Animals↗
PubMed1985

Inhibition of fumarase by S-2,3-dicarboxyaziridine.

S-2,3-Dicarboxyaziridine was found to be a potent competitive inhibitor (Ki = 0.08 microM) of fumarase from pig heart. The aziridine did not inactivate the enzyme or exhibit any observable substrate activity. It is likely that it functions as a transition state analogue mimicking the carbanion intermediate found in the normal catalytic reaction. The aziridine inhibited fumarate utilization in ruptured but not intact mitochondria.

Aziridines↗
PubMedDate not supplied

[Incidence of chromosome aberrations in hothouse workers and the in vitro sensitivity of their lymphocytes to the cytogenetic action of dimatif].

The cytogenetical survey of eight persons working in greenhouse and occupationally contacting with a complex of pesticides has shown a significant increase of chromosomal aberration level in comparison with the control group. It is determined that the cytogenetic effect of the greenhouse's workers differed significantly from that of the control group when lymphocytes of the examined persons were treated by the potent mutagen dimatyph in vitro. The occupational group on the whole was more sensitive than control persons to the clastogenic action of dimatyph (43.0 +/- 2.2 and 28.7 +/- 2.4%, respectively). An assumption is advanced on the modifying influence of the pesticide complex on the frequency of induced chromosomal aberrations in vitro.

Adult↗
PubMed1985

[Antitumor activity and pharmacological properties of furizil].

The paper discusses the biological properties of 2-(2-furyl)-5-oxymethyl-5-(2,4-diethyleneimino-1,3,5-triazine- 6-yl) amino-1,3-dioxane (furizil), synthesized by substituting ethyleneimine groups for chlorine atoms in individual stereoisomer of a dichlorotriazine derivative. Furizil was found to inhibit the growth of Ehrlich's tumor, Walker's carcinosarcoma, sarcoma 45 and rat ovarian tumors, the inhibition rate ranging 76-100%. Parenterally administered, LD50 appeared to be 6 mg/kg for rats and 15 mg/kg for mice. Studies of chronic toxicity established damaging effects of furizil on hematopoietic, gastrointestinal and reproductive organs. Toxic effects subsided 1-2 weeks after the drug withdrawal.

Animals↗
PubMedDate not supplied

[Effect of phosphemide in combination with dexamethasone on DNA structure in sarcoma 45].

It is shown that under the influence of phosphemide in combination with dexamethasone some characteristics of tumour DNA (content of 5 methyl cytosine, temperature, interval and enthalpy of melting) approximate the corresponding characteristics of DNA of healthy animals' liver better than under the influence of phosphemide only.

5-Methylcytosine↗
PubMed1985

[Experimental study on immunochemotherapy (PSK, CQ) in rat bladder cancer (BC-47)].

Cancer of the urinary bladder is a tumor with the highest frequency among urogenital cancers, and more-over, its recurrence rate is high. It is considered important and urgently necessary to conduct studies into the prevention of recurrence of this cancer. We have started a Study Group on Postoperative Maintenance Therapy for Bladder Tumor (Tokyo), and conducted group studies on the prevention of recurrence. Fundamental experiments have been performed, and the following results obtained. Antitumor effects of PSK in combination with CQ for bladder carcinoma were studied using male ACI rats. An established bladder carcinoma cell line, BC47 was transplanted into the backs of rats subcutaneously prior to the administration of PSK and CQ. Inhibitory effect on tumor growth and prolongation of survival period were examined. Although single-agent PSK or CQ both had inhibitory effects on transplanted tumors as well as on metastatic tumors in the lung, more remarkable effects were noticed as a result of combination treatment. Prolongation of lifespan using combination therapy was superior to that using single treatment and the rats of decrease in body weight was also lower. These results do not necessarily clarify the antitumor mechanisms, but the immune system, probably non-specifically, may take part in the mechanism judged from the accumulated results obtained from in vivo systems. We think that the combinational effects of these two drugs on general condition are probably originated from inhibition of tumor growth since the inhibition, prolongation of lifespan, change of body weight and so on were closely correlated with each other. However, the direct effect of these drugs may also be counted. The combination therapy of PSK and CQ seemed to be useful against rat bladder carcinoma, BC47. We therefore intend to proceed with group study trials of Postoperative Maintenance Therapy for Bladder Tumor.

Animals↗
PubMed1985

Topical chemotherapy of intradermal Walker 256 carcinosarcoma with diaziquone and doxorubicin in the rat.

A model for metastatic skin cancer using intradermal injection of Walker 256 carcinosarcoma has been developed in the rat. Using this model, antitumor activity of topically applied doxorubicin and diaziquone in Vanicream, Plastibase, and dimethyl sulfoxide (DMSO) as vehicles was compared with intraperitoneal injection of the drugs at the same doses beginning 4 days after injection of tumor cells. Doxorubicin applied topically at 0.5 mg/day for 4 days in Vanicream or Plastibase exhibited no antitumor activity, while i.p. administered doxorubicin at 0.5 mg/day for 4 days inhibited tumor growth at day 20 by 66%. Diaziquone applied topically at 0.1 mg/day for 4 days in Vanicream, Plastibase, or DMSO inhibited tumor growth at day 20 by 66, 86, and 43%, respectively, and cured animals of the skin tumor at a dose of 0.5 mg/day. Diaziquone administered i.p. at 0.5 mg/day for 4 days was lethal to rats, and at 0.1 mg/day it produced 93% inhibition of tumor growth at day 20. Diaziquone applied topically at 0.1 mg/day for 4 days in Plastibase cured rats of advanced tumor when treatment was begun 12 days after injection of tumor cells. The area under the plasma radioactivity time curve over 5 h for a single 0.64-mg dose of topically applied [ring-14C]diaziquone in DMSO was 0.01% that of the same dose of [ring-14C]diaziquone administered i.p. in non-tumored rats. The decrease in WBC count following topical application of diaziquone at a dose of 0.1 mg/day for 4 days, compared to the same dose of diaziquone administered i.p., was 62% in Vanicream, 81% in Plastibase and 33% in DMSO. Topical diaziquone was non-toxic to normal skin in the rat and in the domestic pig. It is concluded that topical application of diaziquone offers a therapeutic advantage over systemic treatment for metastatic cancer of the skin.

Absorption↗
PubMed1985

[Synthesis of tritium-labeled N,N-dimethyl-2-phenylaziridinium and its reaction with acetylcholinesterase].

The synthesis of tritium-labeled N,N-demethyl-2-phenylaziridinium has been described. The specific radioactivity of the product obtained was 1,06 TBq/mmole. Kinetics of incorporation of this radioactive label into acetylcholinesterase of cobra venom (Naja naja oxiana) has been studied at 1,05 mM ligand concentration (25 degrees C, pH 7,50. 0,15 M phosphate buffer). Under these conditions two molecules of the radioactive label have been found to react with the enzyme. One molecule incorporates fast with half-life of 4,8 min, not affecting the enzymatic activity. Incorporation of the second label is a slow reaction with half-life of 6 hr and leads to complete inactivation of acetylcholinesterase. Molecular mass of the modified enzyme is 63 +/- 4 kDa and coincides with that of native one.

Acetylcholinesterase↗
PubMed1985

Pharmacokinetics of diaziquone after three different dosage regimens.

Diaziquone (AZQ) is a benzoquinone derivative exhibiting significant effects against CNS tumors. This study investigates the pharmacokinetics of AZQ for three different durations of continuous iv infusions, over 20 mins, 4 hrs, and 6 hrs, in nine patients with CNS malignancies. Total AZQ doses varied from 10 to 20 mg. The average elimination half-life was 37.2 +/- 13.9 mins, the total clearance was 515 +/- 280 ml/min or 11.3 +/- 5.9 ml/min/kg, and the apparent volume of distribution by area was 26.5 +/- 14.7 L or 0.62 +/- 0.50 L/kg. Peak concentrations after the 20-min infusions (three patients) varied from 0.58 to 1.20 micrograms/ml, whereas concentrations during the 4-hr infusions (three patients) varied from 0.02 to 0.37 micrograms/ml, and during the 6-hr infusions (three patients) varied from 0.02 to 0.61 micrograms/ml. These results indicate that concentrations found to exhibit minimum inhibitory effects in in vitro cell studies are achievable during prolonged iv infusions of AZQ.

Antineoplastic Agents↗