[Anti-nitrosative system as a factor of malignant tumor resistance to cytotoxic effect of nitrogen monooxide].

The inhibitory action of binuclear dinitrosyl iron complexes with glutathione on the growth of implanted solid tumor in BDF1 mice bearing Lewis lung carcinoma cells was found. The effect was induced by intraperitoneal injection of the binuclear dinitrosyl iron complexes to mice at a dose of 200 µM/kg daily on days 1-5 and 7-11. At the binuclear dinitrosyl iron complexes: free glutathione ratios of 1:1; and 1:10 in solutions, the inhibitory effect of the DNICs reached the level of 70% and 85%, respectively. When B-DNICs were not further infused, intensive tumor growth, a more rapid rate of tumor growth than control, was observed. The selective accumulation of DNICs as well as iron nitrosyl complexes of heme-containing proteins in tumors were detected by EPR method. The latter were found also in the tumors in control animals. Tumor growth delay in course of B-DNIC administration to the mice is supposed to be due to the elaboration of anti-nitrosative defense in tumor tissue in response to the action of NO released from B-DNIC.

[Polyacrylates of noble metals as potential antitumor drugs].

The antitumor activity of polyacrylates of the noble metals containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) has been studied using experimental murine solid tumor models (Lewis lung carcinoma and Acatol adenocarcinoma). It has been found that polyacrylates of the noble metals are capable of inhibiting tumor development by 50-90% compared to control. Auracryl that inhibites the growth of Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90%, respectively, compared to control is the most efficient among the tested compounds and can be recommended for the further profound preclinical studies.

[Anti-tumour activity of dinitrosyl iron complexes with glutathione].

The anti-tumour dose-dependent effect of binuclear dinitrosyl iron complexes with glutathione as NO donors on solid tumour in the mouse Lewis lung carcinome was detected. The complexes being injected at the doses of 21, 42, 105 mg/kg daily during 10 days blocked completely the development of the tumour for the first week after tumour cell implantation into animals. After that, the part of tumour cells which remained in intact alive state began to grow at the rate equal to that for control animals. The effect was proposed to be caused via the formation of the anti-nitrosative defense system in the cells as a response to NO attack to cells. It was also hypothesized that this system can be inactivated by higher doses of dinitrosyl iron complexes. The data were obtained which were in line with the hypothesis.

[The sensitivity of experimental tumor systems to ultra low doses of doxorubicin]. / Chuvstvitel'nost' éksperimental'nykh opukholevykh modelei k sverkhmalym dozam doksorubitsina.

Biological effect of doxorubycin in standard (10(-3) mol/l) and ultra low doses (10(-5)-10(-20) mol/l) against some "signal" animal tumor systems--Lewis lung carcinoma, 755 adenocarcinoma, B-16 melanoma, Ehrlich carcinoma and L1210 leukemia was studied. The all models were very sensitive to the action of the drug in standard dose. Solid tumors' growth inhibition by 80-95% as well as increasing in life span of mice with L1210 leukemia by 86% in comparison with control and surviving of animals with Ehrlich carcinoma had been revealed. It had been shown that the drug in the area of ultra low doses occurred the following effects: inhibition of Lewis lung carcinoma growth by 80-95% compared to control after administration of the all tested ultra low doses; increasing of the life span of the animals with Ehrlich carcinoma and L1210 leukemia by 86-123% and 6-23%, correspondingly, upon the action of all tested ultra low doses; inhibition of B-16 melanoma growth by 50 and 70% after administration of the drug in doses 10(-20) mol/l and 10(-5) mol/l, correspondingly as well as deceleration of 755 carcinoma growth by 40% compared to control after action of the drug in the dose 10(-20) mol/l; stimulation of the B-16 melanoma growth by 20% relative to control after 10(-10) mol/l dose injection and enhancement of tumors sizes by 20-60% above control levels as a result of treatment of mice with 755 carcinoma by the drug in such ultra low doses as 10(-5) and 10(-15) mol/l. So, it was found that all tested tumor systems revealed certain sensitivity to the some ultra low doses of the drug. At the same time it was shown that doxorubycin in ultra low doses displayed alternative character of its biological effect, directivity of which varied according with the dose level and tumor strain.

[Antitumor effect of joint action of low intensity electromagnetic fields and ultra low doses of doxorubicin]. / Protivoopukholevaia éffektivnost' sovmestnogo vozdeistviia nizkointensivnogo élektromagnitnogo polia i sverkhmalykh doz doksorubitsina.

Combined action of a low intensive physical factor and a chemotherapeutic agent in ultralow doses against Lewis lung carcinoma was studied. Antitumor activity of low intensiwe electromagnetic field was expressed as inhibition of tumor growth at 60% compare to control. Ultra low doses of doxorubicin as well as its standard dose resulted in inhibition of tumor growth by 60-70% in comparison with control. Joint action of both factors leaded to increasing in the antitumor effect that reached such level of tumor growth inhibition as 85% relative to control.

[Taxotere and methylnitrosourea: experimental appraisal of combination chemotherapy]. / Taksoter i nitrozo metilmochevina: élsperimental'naia otsenka éffektivnosti sovmestnogo primeneniia.

The effectiveness of taxotere and methylnitrosourea (MNU) combined application against murine P388 leukemia has been studied. Antitumor drugs were administered separately or in combination in doses of 50, 60 or 70 mg/kg per day, i/p, beginning from day 1 after tumor transplantation. Combined administration was shown to potentiate antitumor effect, which also largely depended on schedule. Survival increase varied within 50-130% of control values. Optimal effect was observed with the following schedules: taxotere + MNU, 24-hour interval between injections, and MNU-taxotere, 4-day interval between injections. Synergism was in evidence since the therapeutic effect of combination treatment was significantly higher than that of either drug administered alone.

[Comparative study of of natural and radiation-induced aging in mice]. / Sravnitel'noe izucheniie protsessov estestvennogo i radiatsionnogo stareniia myshei.

Aging of female CBA mice was accelerated by irradiation of the head at 10 and 12 Gy. The mean life span was shortened by 10.5 and 21%, respectively. The distribution by life span was similar in the control and experimental groups. The level of DNA oxidation products in the urine was normalized within 28 days after irradiation. At the age of more than 7.5 months, the irradiated mice had a lower body weight. Age-related changes of body temperature in irradiated (10 Gy) and control mice mostly coincided; the differences were evident after 18 months. It was concluded that physiological and radiation-induced aging are significantly similar.

[A comparative study of the action of 1-methyl-1-nitrosourea and 1,3-dimethyl-1-nitrosourea on tumor cell DNA in vitro and in vivo by the alkaline elution method]. / Sravnitel'noe izuchenie deistviia 1-metil-1-nitrozomocheviny i 1,3-dimetil-1-nitrozomocheviny na DNK opukholevykh kletok in vitro i in vivo metodom shchelochnoi éliutsii.

DNA damage of the tumor cells was studied by the method of alkali elution from filters after introduction of 1-methyl-1-nitrosourea (MNU) and 1,3-dimethyl-1-nitrosourea (DMNU) to mice with Ehrlich ascites carcinoma or after treatment of the cultivated cells with these drugs. DNA was essay fluorometrically using DAPI. The degree of DNA damage was characterized by the constant of the alkali elution rate (Kae), which was estimated according to the anamorphism of the kinetic curves of elution. It was shown that in the case of MNU application the tumor cell DNA was damaged to a greater extent than in the case of DMNU application. Kae increased with the concentration of drugs. A correlation was established between the antitumor activity of the drug (kappa), K(ae), and the number of chromosome defects per cell (gaps, deletions, microfragments, ring chromosomes, and translocations). This suggests that kappa is due both to DNA damage and chromosome defects.

[Structural and biochemical parameters of blood components of mice after gamma irradiation with small doses of different intensity]. / Strukturnye i biokhimicheskie pokazateli élementov krovi myshei posle gamma-oblucheniia v malykh dozakh raznoi intensivnosti.

The complex study on the low gamma-irradiation on the structural feature of lymphocyte DNA and lipid peroxidation (LPO) regulatory system parameters in mice blood was carried out depending on irradiation intensity. It was found that DNA alkaline elution rate constants, viscosity of the different regions of erythrocyte membranes and LPO products content in mice blood plasma varied nonlinearly depending on dose or dose rate. The proportion of the damage types and the range of the DNA structural changes substantially differ depending on the gamma-irradiation dose and its intensity. It is considered that the proportion of the DNA and membrane damage and repair can change depending on radiation dose and dose rate.