[New approaches to the drug prophylaxis of mammary tumor: evaluation of the prophylactic effect of lovastatin and captopril in rats with experimental mammary gland tumors].

Effects of the GABA-CoA reductase inhibitor lovastatin and the ACE inhibitor captopril on the induction and growth of mammary gland tumors induced by N-methyl-N-nitrosourea in Wistar rats have been studied. It is established that lovastatin administered in a doze of 80 mg/kg two times a week exhibits anticarcinogenic activity, which is manifested by a significant decrease in the incidence of neoplasms and an increase in the survival lifetime in the experimental animals. Captopril administered in a doze of 50 mg/kg two times a week significantly decreased the tumor growth rate. The chemopreventive activity of these drugs can be due to their possible regulatory influence on the processes of cell proliferation, differentiation, neoangiogenesis, and apoptosis. The results of this investigation show good prospects for the further investigation of lovastatin and captopril as chemotherapeutic agents for the prophylaxis of mammary tumor.

[Carcinogenic activity of a 4,4-diaminobiphenyl ester]. / O kantserogennoi aktivnosti 4,4-diaminodifenilovogo éfira

4,4'-diaminodiphenyl ether (dadpe) was injected subcutaneously (once a week) or given per orally (1-5 times a week) in rats in a dose of 25 mg/per rat and in mice of line CC57W in a dose of 5 mg/per mouse. Administration of the substance produced in mice and rats under study renal lesions of the nephrosis type with a nephritic component. In later stages of the experiment some rats showed adenomatous regeneration and formation of renal cysts, in one rat hypernephroid cancer of the kidney was observed. Tumors of different localizations were found in 44% of rats (in 7 of 16 animals), and in 57% of mice (in 8 of 14 animals) in experiments with peroral administration of the substance; in 18% of rats (in 7 of 39 animals) and in 33% of mice (in 3 of 9 animals) in experiments with subcutaneous injection of the substance. The results of the experiments have evidenced an insignificant blastomogenic action of 4,4'-diaminodiphenyl ether.

[Effect of glucuronic acid on the carcinogenic action of urethane, dibutylnitrosamine and 7,12-dimethyl[A]anthracene]. / Vliianie gliukuronovoi kisloty na kantserogennoe deistvie uretana, dibutilnitrozamina i 7,12-dimetilbenz[A]antratsena.

C57W and SHR mice were given intraperitoneal injections of 100 or 300 mg/kg body weight glucuronic acid (in isotonic NaCl solution) 15-30 minutes prior to treatment with urethan, dibutylnitrosamine or 7,12-dimethyl-1,2-benzanthracene. This resulted in a lower carcinogenic effect on the lung and the incidence of lung adenoma was half that registered in the animals who had received a carcinogen only.

[Prevention using ascorbic acid, hexamethylenetetramine and sodium metabisulfite of the blastomogenic effect caused by the combined administration into the stomach of mice of sodium nitrite with methylurea or with aminopyrine]. / Preduprezhdenie s pomoshch'iu askorbinovoi kisloty, geksametilentetramina i metabisul'fita natriia blastomogennogo éffekta, vyzvannogo sovmestnym vvedeniem v zheludok mysham nitrita natriia s metilmochevinoi ili s amidopirinom.

It was shown in experiments on 186 mice that formation of tumors of the lung and fore-stomach induced by injection of sodium nitrite in combination with aminopyrine or methylurea is inhibited following treatment with ascorbic acid, hexamethylenetetramine or sodium metabisulfite.

[The relationship between the activity of microsomal enzymes and pulmonary carcinogenesis in mice]. / Zavisimost' legochnogo kantserogeneza u myshei ot aktivnosti mikrosomal'nykh fermentov

Under study was the effect of phenobarbital, medinal and aminazine on the development of lung tumors in mice, as well as on the content of cytochrome P-450 in rat liver microsomes. Phenobarbital and medinal administration resulted in a 2-8 fold increase in cytochrome P-450 amount. Aminazine would reduce the latter but insignificantly. The number of urethan induced lung adenomas in mice was reduced by 64 per cent in phenobarbital exposure while medinal yielded only the decrease by 25-44 per cent. Aminazine failed to effect urethan carcinogenesis. Medinal would also suppress the development of DMBA induced lung tumors in mice by 34 per cent, but MC-by 50 per cent.

[Effect of guanine and guanosine-2',3' phosphate on sarcolysin-H3 binding to the DNA of rat liver]. / Vliianie guanina i guanozin-2',3' fosfata na sviazyvanie sarkolizina-H3 s DNK pecheni krys

Rats were injected sarcolysin-H3 in a dose of 200 or 500 mC per rat. In animals sacrificed 30, 60 and 90 minutes following sarcolysin-H3 injection an increased radioactivity of DNA was noted that indicates binding of sarcolysin-H3 or its labelled derivatives to DNA. Guanine or quanosine-2', 3' monophosphate injected in animals decreased binding of sarcolysin-H3 to the rat liver DNA (maximum reduction of DNA radioactivity in 47%). In the experiments in vitro guanosine-2', 3' phosphate inhibited sarcolysin-H3 binding to DNA isolated from E. coli. A protective effect of quanine and guanosine-2', 3' phosphate with respect to DNA alkylation seems to be considerably conditioned by a competitive action of these nucleophils.

[Effect of nucleophilic compounds on sarcolysine-3H and DMNA-14C binding with DNA]. / Vliianie nekotorykh nukleofil'nykh soedinenii na sviazyvanie sarkolizina-3H i DMNA-14C s DNK.

The authors have studied the effect of adenine, adenosine, guanosine, cytidine and cysteine on sarcolysine-3H binding to DNA in vivo (rat liver) an in vitro and DMNA-14C binding in vivo. It was shown that among the compounds under test adenine, adenosine and guanosine rendered a marked protective effect with relation to DNA alkylation, which is likely to be due to their nucleophilic properties.

[The relationship between stomach tumor development in mice and DMBA distribution]. / Zavisimost' vozniknoveniia opukholei zheludka u myshei ot raspredeleniia DMBA

The character of blastomogenic action of 7,12-dimethylbenz(a)anthracene on the stomach in its parenteral administration was studied on different lines of mice. Under the same conditions DMBA distribution was investigated in the proventriculus and gastric glandular tissues. In DMBA application on mice skin oin the dosage of 0.05 mg per animal in 0.1 ml of acetone proventricular tumors developed in 34% of mice of line CC57Br, in 10% of mice of line CC57W, and in 11% of mice of line C3HA, and in 19% of white nonpedigree mice. In intraperitoneal injection of DMBA in the dose of 0.5 mg per mouse in 0.2 ml of saline solution proventricular tumors appeared in 56% of CC57Br mice (in 9 of 16) and in one of five mice of CC57W line. Whereas, in application of DMBA onto mice skin in the dose of 0.5 mg per mouse in 0.1 ml of acetone the DMBA content in the proventriculus was 13 times higher than that in gastric glandular tissues.

[The effect of N-nitrosomethylurea on organ cultures of human embryonal lung tissue]. / Deístvie N-nitrozometilmocheviny na organye kul'tury émbrional'noí tkani cheloveka

The character of blastomogenic action of 7,12-dimethylbenz(a)anthracene on the stomach in its parenteral administration was studied on different lines of mice. Under the same conditions DMBA distribution was investigated in the proventriculus and gastric glandular tissues. In DMBA application on mice skin in the dosage of 0.5 mg per animal in 0.1 ml of acetone proventricular tumors developed in 34% of mice of line CC57Br, in 10% of mice of line CC57W, and in 11% of mice of line C3HA, and in 19% of white nonpedigree mice. In intraperitoneal injection of DMBA in the dose of 0.5 mg per mouse in 0.2 ml of saline solution proventricular tumors appeared in 56% of CC57Br mice (in 9 of 16) and in one of five mice of CC57W line. Whereas, in application of DMBA onto mice skin in the dose of 0.5 mg per mouse in 0.1 ml of acetone the DMBA content in the proventriculus was 13 times higher than that in gastric glandular tissues.

[Study of the role of the feeding factor in the development of induced experimental mammary cancer in rats]. / Izuchenie roli faktora pitaniia v razvitii indutsirovannogo raka molochnoi zhelezy v éksperimente u krys.

It is studied the influence of two types of experimental diets on rats origin mammary tumors. The first diet was enriched by pig's fat and 2nd diet contained soybean protein and induced N-nitrozo-N-methylurea (MNM). The tumors of rat's mamma were induced by intramammary injections of N-nitrozo-N-methylurea in area of the 2nd left mamma in dose 2.5 mg per rat once a week during 5 weeks. The rats of control group were not exposed to any additional influences except for a carcinogenic one. The rats of first and second subgroup were fed with lard (50 mg/kg) and soybean protein (200 mg/kg) during 30 weeks. It was shown that lard evinced cocarcinnogenic action on the origin of mammary tumors to stimulating their growth and development while the soybean protein considerably reduced frequency of mammary tumors and slowed the time of their appearance.

Effects of acetylsalicylic acid and celecoxib on the N-nitrosodiethylamine induced carcinogenesis in rat liver and esophagus.

The effects of nonsteroid antiinflammatory drugs (acetylsalicylic acid and celecoxib) on N-nitrosodiethylamine-induced carcinogenesis in the liver and esophagus were studied in rats. The inhibitory effect of celecoxib on carcinogenesis was more pronounced (in comparison with acetylsalicylic acid), which manifested in a significantly decreased incidence of neoplastic changes in the liver tissue (from 91.7 to 65.2%), number of tumors in the esophagus (from 4.13 to 2.61 tumor/rat), and in delayed malignization in the liver and esophagus. The incidence of erosions and ulcers of the gastric mucosa was significantly lower after celecoxib treatment. These data indicate that celecoxib inhibits N-nitrosodiethylamine-induced carcinogenesis in the liver and esophagus.

[Inhibitory effect of a number of substances on manifestation of the embryotoxic and teratogenic effects of methylurea and sodium nitrite]. / Tormoziashches vliianie riada veshchestv na proiavlenie embriotoksicheskogo i teratogennogo deistviia metilmocheviny i nitrita natriia

Embryos died and a teratogenic effect followed combined intragastric administration of methylurea (MU) and sodium nitrite (SN) to rats on the 9th day of pregnancy; this was caused by the endogenous synthesis of nitroso-methylurea which produced a pathogenic action. Ascorbic acid and urotropine completely blocked the possibility of manifestation of the embryotoxic and teratogenic effect occuring after combined administration of MU and SN. Sodium sulfomate decreased the embryotoxic and partially the teratogenic effect considerably, whereas urea failed to prevent the expression of the harmful effect of MU and SN on the embryo.