[The effect of the time of methotrexate administration over 24 hours on the antitumor activity of the preparation, its concentration in the blood and in the tumor in Pliss' lymphosarcoma in rats]. / Vliianie vremeni vvedeniia metotreksata v techenie sutok na protivoopukholevuiu aktivnost' preparata, ego kontsentratsiiu v krovi i opukholi pri limfosarkome Plissa u krys.

A mismatch between a circadian rhythm of blood-methotrexate level and that of the drug concentration in rat transplanted lymphosarcoma tissue was established. The drug proved 3 times more effective when given at the time of the day when its concentration in tumor tissue was likely to be the highest.

[Tumor progression as a factor of variability of diurnal rhythm of phosphorus metabolism in a tumor]. / Opukholevaia progressiia kak faktor variabel'nosti struktury sutochnykh kolebanii fosfornogo obmena v opukholi.

In a transplanted lymphosarcoma of rats by means of Cosinor method we discovered rhythm of P32 inclusions with ultradian and circadian periods. In the course of tumor growth changes of spectrum of periods, amplitudes and acrophases of rhythms take place. These shifts are explained by the progression and clonal structure of neoplasms.

[The prevention of the side effects of cytostatics by administering them at various times of day]. / Profilaktika pobochnogo deistviia tsitostatikov putem ikh vvedeniia v razlichnoe vremia sutok.

Rats bearing Pliss' lymphosarcoma revealed diurnal variations of body temperature. Cyclophosphamide and methotrexate were significantly less toxic when injected at peak temperatures than at minimal ones.

[Potentiation of the radiosensitizing effect of metronidazole using whole-body drug-induced hyperthermia]. / Usilenie radiosensibiliziruiushchego éffekta metronidazola pri pomoshchi obshchei medikamentoznom gipertermii.

The total drug hyperthermia in the presence of metronidazole administration improves radiotherapeutic results in Pliss lymphosarcoma: tumor growth inhibition increases by 12.7-18.5%, tumor regression by 30.6-38.9%. A dose of 100 mg/kg of metronidazole combined with irradiation in the presence of moderate hyperthermia produces even a more noticeable radiosensitizing effect than a dose of 700 mg/kg without hyperthermia. A possibility of quite a high level of tumor radiosensitization with lower doses of metronidazole without toxic manifestations of the body was shown.

[Accumulation of metronidazole in tumors during whole-body hyperthermia induced by Sulfazin]. / Nakoplenie metronidazola v opukholi pri obshchei gipertermii, vyzvannoi sul'fazinom.

A study was made of metronidazole accumulation in the blood of animals and tumorous tissues of Pliss lymphosarcoma after the total moderate hyperthermia caused by subcutaneous injection of the pyrogenic drug sulfadiazine. Metronidazole concentration in the blood and tumors of hyperthermized animals was 2-3 times as high as in those of the control animals. A time shift of the maximum values of metronidazole accumulation occurred in hyperthermia. Under normal conditions the peak of accumulation was observed 2 h after the administration of the radiosensitizer whereas in hyperthermia depending on its duration it could develop 1 h earlier. Thus the total moderate hyperthermia served as a favorable background for raising metronidazole concentration in tumor opening up prospects for potentiating the radiosensitizing effect of metronidazole and perhaps some other means in the utilization of small nontoxic doses of the drug.

[Circadian rhythm of adenosine triphosphatase activity and 32P content in Pliss lymphosarcoma]. / Sutochnyi ritm aktivnosti adenozintrifosfataz i soderzhaniia 32P v limfosarkome Plissa.

Within a daily period maximal activity of ATPases and content of 32P in Pliss lymphosarcoma tissue was found in the samples taken at 15 or 21 p.m. and 3 a.m. The radioactivity in the tumor was minimal between 9 and 12 a.m. and 18 or 24 p.m. The alterations in Mg2+-ATPase activity in their magnitude and circadian rhythm coincided completely with the daily variations in content of radiophosphorus. Activities of Na+, K+- and HCO(3-)-ATPases exhibited maximal values at 15 p.m. and, especially between 3 and 6 a.m., i.e. these alterations were of two-peak shape without the peak at 21 p.m.

[Effect of the combined action of metronidazole and cycloheximide on protein synthesis and tumor regression following irradiation]. / Vliianie kombinirovannogo deistviia metronidazola i tsiklogeksimida na sintez belka i regressiiu opukholi posle oblucheniia.

A radiosensitizing effect of metronidazole on a tumor was enhanced by a small dose of cycloheximide. Metronidazole caused a considerable inhibition of the protein synthesis during the first six hours following irradiation. Cycloheximide, in the dose used, did not enhance the effect of metronidazole on the postirradiation protein synthesis.

[Sulfazin in the thermoradiotherapy of experimental tumors]. / Sul'fazin v termoradioterapii éksperimental'nykh opukholei.

A possibility of radiosensitization of Pliss' lymphosarcoma and tumor RS-1 by using general hyperthermia with sulfazin was studied. Subcutaneous transfusion of sulfazin to rats caused a rise of the body temperature by 2-2.5 degrees C on the 2nd day after injection with the upkeep of hyperthermia for 3 days. A combined effect of sulfazin and irradiation enhanced the retardation of growth rate of tumors and increased their regression. The lifetime of animals increased significantly. A more noticeable postradiation suppression of mitotic activity was observed.