ABSTRACT
Combined chronic treatment of Ehrlich solid carcinoma (EC) with an NOS inhibitor 1-isobutanoyl-2-isopropylisothiourea hydrobromide (T1023) and a PDK1 inhibitor dichloroacetate was accompanied by statistically significant synergetic antitumor effects manifested in a significant and stable suppression of neoplasm growth (by 55-65%). Separate treatment with T1023 and dichloroacetate induced moderate short-term inhibition of tumor growth (by 30-35%) followed by weakening of tumor sensitivity to these substances. These results attest to synergetic antitumor effects NOS inhibitor T1023 and PDK1 inhibitor dichloroacetate producing antiangiogenic and hypoxia-targeted cytotoxic effects, during their combined administration, which allows overcoming the adaptive potential of the tumors.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/enzymology , Dichloroacetic Acid/therapeutic use , Nitric Oxide Synthase/antagonists & inhibitors , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/antagonists & inhibitors , Animals , Cell Line, Tumor , Female , Mice , Thiourea/analogs & derivativesABSTRACT
We studied the effect of T1023, NO-synthase inhibitor, N-acyl-S-alkyl-isothiourea in a single administration at a dose of 75 mg/kg on the growth of transplantable rat sarcoma M-1 and the development of acute skin reactions after the local impact of γ-radiation at the doses of 32 and 36 Gy. The results showed that the T1023 at a single dose had no effect on the growth of sarcoma, and did not modify the radiosensitivity of the tumor and anti-tumor efficacy of γ-rays. However, at both doses T1023 significantly reduced the severity of acute radiation skin reactions. NOS inhibitor did not change the duration of the inflammatory and regenerative processes, but significantly limited the degree of radiation alteration of the deep layers of the skin and underlying tissues. The findings suggest that the hypoxic mechanism of antitumor action allows T1023 to selectively protect the non-malignant tissue during radiation therapy of solid tumors. Therefore, this compound may be regarded as a promising basis for the development of pharmacological prevention of radiotherapy complications.
Subject(s)
Enzyme Inhibitors/administration & dosage , Radiation-Protective Agents/administration & dosage , Sarcoma/drug therapy , Animals , Enzyme Inhibitors/chemical synthesis , Gamma Rays , Humans , Male , Nitric Oxide Synthase/antagonists & inhibitors , Radiation Tolerance/drug effects , Radiation-Protective Agents/chemical synthesis , Rats , Sarcoma/pathology , Sarcoma/radiotherapy , Skin/pathology , Skin/radiation effectsABSTRACT
Oil products are the one out of major pollutants in soil. For reduction of the technogenic load on human beings and performing preventive measures in the Republic of Belarus differentiated hygienic rate setting for oil products in the soil have been scientifically substantiated for follows different categories of Lands: agricultural lands, defense lands, lands for recreation, historical and cultural purpose, forest lands, lands of water fund, reserve lands--50 mg/kg; settlements sand, garden housing and dacha cooperatives,--100 mg/kg; industrial, transport, communication, energy, defense and other appointments lands--500 mg/kg.
Subject(s)
Oils/chemistry , Soil Pollutants/chemistry , Soil/chemistry , Humans , Hygiene , Maximum Allowable Concentration , Oils/isolation & purification , Petroleum/analysis , Republic of BelarusABSTRACT
A Rhodococcus erythropolis 40 phi strain isolated from the soil utilizes 0.1-2% v/v dibutylphthalate (DBP) and di-(2-ethylhexyl)-phthalate (DEHP) as a single carbon source. The strain metabolizes DBP and DEHP via the following steps: diester --> phthalate --> benzoate --> p-hydroxybenzoate --> 3,4-dihydroxybvenzoate --> 3-ketoadipinate.
Subject(s)
Dibutyl Phthalate/pharmacokinetics , Diethylhexyl Phthalate/pharmacokinetics , Plasticizers/pharmacokinetics , Rhodococcus/metabolism , Biodegradation, Environmental , Culture Media , Industrial Waste , Soil Microbiology , Soil Pollutants/pharmacokinetics , Time FactorsABSTRACT
The distribution in environment of phthalic acid esters classified according to their inherent toxicity, teratogenic, mutagenic properties and cancerogenic activity into a group of priority pollutants of biosphere is described in this review. The role of microbial community in degradation of phthalate esters has been demonstrated. The effect of such environmental factors as pH of the medium, temperature, humidity, concentration of organic matter, the introduction of promising microbial strains in natural biocenoses has been examined. The pathways of phthalate ester metabolism have been analysed in representatives of active bacterial destructors belonging to genera Nocardia, Pseudomonas and Micrococcus. The decomposition rate of phthalate esters has been shown to be correlated with structure, concentration and culture conditions.
