The carcinogenic activity of N-nitrosodipropylamine administered perorally to C57Bl mice

187 female and male C57B1 mice received N-nitrosodipropylamine (NDPA) twice a week for 50 weeks by intragastric intubation. The total dose of NDPA administered to groups I and II was 3 mg or 1 mg per mouse. The main kinds of tumours in these groups were tumours of esophagus, forestomach, lungs, and lymphomas. The incidence of pulmonary adenomas and forestomach papillomas was more frequent in the group which received a higher dose of carcinogen.     

Effect of ethanol on N-nitrososarcosine ethyl ester-induced carcinogenesis in the esophageal and forestomach mucosa of mongrel rats

Administration of N-nitrososarcosine ethyl ether (50 mg/kg, per os, every day during 4 months) to rats induced after 8 months multiple tumours (most often papillomas) of oesophagus and forestomach. Total incidence of tumour-bearing animals was 42.4% in oesophagus and 21.2% in forestomach, distribution of tumours being 85.6 and 14.4%, respectively. The combined administration of carcinogen with 40% water solution of ethanol (0.5 ml, per os, every day during 8 months) did not change general incidence and multiplicity of all tumours, but decreased the relative incidence of oesophagus tumours and increased that of forestomach tumours. Possible mechanisms of organotropism shifts are discussed.     

Effect of khingamin on the development of SV40 virus-induced and transplantable tumors in hamsters

Chloroquine was administered to 2-month hamsters inoculated at birth with an oncogenic virus SV-40 which was injected daily in a dose of 30 mg/kg for a month. Chloroquine-treated animals showed a statistically significant (6 weeks) shorter latent period of tumour development. The drug exerted no effect neither on the rate and incidence of transplantable E-1 test tumours or on the phenomenon of resistance in experiments on 4-6-month hamsters under its multiple administration in doses close to maximum tolerated ones (40 mg/kg).     

The pharmacokinetics of the antitumor preparation of dimetinur

The pharmacological disposition of 1,3-dimethyl-1-nitrosourea (dimetinur) in intact rats and animals with Walker carcinosarcoma, glioma 2211, colon adenocarcinoma was studied by the colorimetric assay using an oral drug dose of 100 mg/kg. Computer analysis of data was based on a single-compartment model using the area under the concentration-time curve (S) and the intact drug half-life (t1/2) as main pharmacokinetic parameters. The highest level of the drug (S) was observed in tumour and brain tissues on an equality with drug distribution between blood, spleen, kidney and lungs. The half-life of the dimetinur removal from blood exceeds the known values for certain active NAM type. The antitumour activity of the drug against the studied tumours correlates positively with pharmacokinetic parameters for the tumours (S and 1/tmax).     

Effect of immunization with tularemia vaccine on 3,4-benz[a]pyrene-induced blastomogenesis and mutagenesis in rats

The living tularemia vaccine is studied for its effect on rat tumours and chromosome aberrations in bone marrow cells during 3,4-benz(a)pyrene injection (BP). It is established that a single epicutaneous vaccination of rats decreases the incidence of BP-induced tumours, prolongs the latent period and reduces the mean weight of tumours as well as lowers the number of myelocaryocytes with chromosome aberrations when BP is administered 15 days after immunization. 125 days after a single subcutaneous injection of BP in a dose of 4 mg the tumours appeared in 57% of animals and in 35% of preliminarily immunized animals. 24 h after intraperitoneal administration of 4 mg of BP the immunized rats revealed a 35% decrease in the amount of chromosome aberrations in myelocaryocytes as compared to the nonimmunized rats.     

Effect of correcting liver function on the development of DMBA-induced mammary gland tumors and the metabolism of sex steroid hormones in rats

The tumours of mammary glands in Wistar rat females were induced by threefold intravenous administration of 7,12-dimethylbenz (a) anthracene (DMBA). The application of pharmacological preparations contributing to the liver function correction (PCLF) in the process of carcinogenesis and during the surgical treatment of mammary tumours leads to prolongation of the first tumour latent period after DMBA administration and of recurrent tumours after the operation. The lowering of the frequency, multiplicity and the rate of mammary tumours growth were also observed. The use of PCLF exerted a normalizing effect on the level of sex steroid hormones in rats.     

Effect of thiamine and its antimetabolite oxythiamine on the proliferative activity of carcinosarcoma Walker 256 cells

The microscopic studies of tumours from rats injected with thiamine at a dose of 20 mg/kg for 5 days have shown that sites of hemorrhages and necrosis are considerably more extensive than in tumours of control animals. Injections of the same doses of oxythiamine increase the rate of pathologic mitoses in tumour cells and decrease the tumour weight by 45%, limit the synthesis of thiamine diphosphate and inhibit the transketolase activity in tissues.     

Effect of BCG vaccination on the incidence of the development of 90Sr-induced osteosarcomas in rats

The frequency of 90Sr-induced osteosarcoma development was determined in the mongrel rats subjected to BCG vaccination. Injection of BCG (5 mg per animal) is shown to change the frequency of tumour development and their multiplicity only in male rats which were vaccinated 20 days before nuclide administration. An increase up to 10 mg per animal of BCG dose injected 10 days before 90Sr administration caused the carcinogenesis inhibition irrespective of the sex of the animals.     

Effect of the duration of administration of 1,2-dimethylhydrazine on its carcinogenic effect

The (CBA x C57Bl)F1 female mice were treated with weekly injections of 1,2-dimethylhydrazine (DMH) at a dose rate of 4.15 mg/kg of body weight during different time periods. Relations between the incidence of organ specified particular tumours depend on the total DMH dose. Incidence of haemoblastoses decreases with an increase in the DMH dose. Dose relationships of the tumour incidence are analyzed statistically by the method with intercurrent mortality corrections and carcinogen effect expressed by relations of the observed and expected numbers.     

Effect of disordered thyroid function on the realization of the transplacental carcinogenic action of N-nitrosomethylurea in 1st- and 2d-generation rats

The F1 rats subjected to the influence of N-nitrosomethylurea (NMU) in dose of 20 mg/kg on the 21 day gestation as a result of postnatal disturbances of the thyroid function induced by long administration of thyroxin (3 mg/100 g, daily), methylthiouracil (MTU; 0.1% solution in tap water) or thyroidectomy have shown a decreased incidence of the nervous system tumours, but not of the kidney tumours, i. e. sites typical of NMU transplacental carcinogenesis. At the same time the NMU transplacental effect increased thyroid carcinogenesis, induced by the MTU postnatal application, which manifested in the increased incidence of malignant tumours of this site. The carcinogenic effect was observed in F2 rats, while some of them developed tumours of the nervous system (14.9%) and kidney (8.5%) but with lower incidence than in F1 (35.4; 14.1%, respectively). The same modifying factors (thyroxin, thyroidectomy, MTU) employed under the same conditions produca similar effect on carcinogenesis in F2 animals.     

Carcinogenic effect of N-nitrosodimethylamine after application to rat skin

A pronounced carcinogenic action was detected after ten-fold application of nitrosodimethylamine in 3 doses (calculated doses equal 10.0; 5.0; 1.0 mg per rat). The tumour incidence in groups is equal to 93.3%, 20.0%, 6.6% and 3.3% (in control). No morphological changes were found in the place of application. Induced tumours localized in the liver, lungs and kidneys.     

Brain tumour development in rats exposed to electromagnetic fields used in wireless cellular communication

It has been suggested that electromagnetic fields (EMF) act as promoters late in the carcinogenesis process. To date, however, there is no convincing laboratory evidence that EMFs cause tumour promotion at nonthermal exposure levels. Therefore the effects of exposure to electromagnetic fields were investigated in a rat brain glioma model. Some of the exposures correspond to electromagnetic fields used in wireless communication. Microwaves at 915 MHz were used both as continuous waves (1 W), and pulsemodulated at 4, 8, 16 and 217 Hz in 0.57 ms pulses and 50 Hz in 6.67 ms pulses (2 W per pulse). Fischer 344 rats of both sexes were used in the experiments. By stereotaxic technique rat glioma cells (RG2 and N32) were injected into the head of the right caudate nucleus in 154 pairs of rats, exposed and matched controls. Starting on day 5 after inoculation, the animals were exposed for 7 hours a day, 5 days a week during 2–3 weeks. Exposed animals were kept unanaesthetized in wellventilated TEM cells producing 915 MHz continuous or modulated microwaves. Their matched controls were kept in identical TEM cells without EMF exposure. All brains were examined histopathologically and the tumour size was estimated as the volume of an ellipsoid. Our study of 154 matched pairs of rats does not show any significant difference in tumour size between animals exposed to 915 MHz, and those not exposed. Thus our results do not support that even an extensive daily exposure to EMF promotes tumour growth when given from the fifth day after the start of tumour growth in the rat brain until the sacrifice of the animal after about 16 days.     

Kinetics of the cell population in adenocarcinoma 755 after cyclophosphane administration and rate of tumor growth after an additional course of therapy with cyclophosphane and 6-mercaptopurine

The two injections of cyclophosphane (100 mg/kg) to mice with adenocarcinoma 755 on the 6th and 11th days after tumour transplantation had no influence on the cell cycle but induced a decrease of its growth rate due to an increase in the level of cell losses. The third cyclophosphane injection (the same dose) on the 17th day after the tumour transplantation or an additional course of five 6-mercaptopurine injections (50 mg/kg each dose) did not change essentially the growth rate of tumours.     

Dependence of the incidence of the occurrence of ovarian and uterine tumors in rats on the irradiation dosage from accelerated particles and gamma rays

The incidence rate of ovarian and uterine tumours in rats after irradiation by protons with the energy of 645 MeV, 9 GeV and He2+ has been studied. The tumour rate is shown to increase with the radiation dose. The character of the dose-response for tumours of two sites is different. A relative risk of ovarian tumour incidence after He2+ exposure is twice as high as after other types of radiation.     

Effect of glucose on fetal weight and the transplacental blastomogenic effect of N-nitrosomethylurea in rats

The N-nitrosomethylurea (NMU)-induced transplacental blastomogenesis in rats was studied under the effect of pre- and postnatal glucose administration. On the 21st day of pregnancy NMU (20 mg/kg) was intraperitoneally administered to rats. From the 7th day of pregnancy experimental rats were treated with 10% glucose solution instead of drinking water, and during 1.5 months after delivery they and their progeny were given 5% glucose solution. The foetal weight in glucose-treated pregnant rate increased. A significant increase of tumour frequency was detected in the progeny of these rats. In male progeny tumours of the nervous system and kidneys typical of NMU effect prevailed and in females--tumours of other organs and tissues, particularly of the mammary gland, pituitary and hemopoietic system. Possible mechanisms of the modifying effect of glucose on the transplacental blastomogenic action of NMU are discussed.     

Local blood flow into tumors during artificial hyperglycemia

The blood flow in the rat Guerin carcinoma was measured by the hydrogen clearance method. It was shown that the blood flow in the tumour tissue decreased almost 3.5 times to the 3 hours of the intravenous glucose infusion at a dose of 80 mg X kg-1 X min-1. In some tumours the microcirculation ceased completely. The results obtained help developing the new schemes of local hyperthermia and induced hyperglycemia in the complex antitumour therapy.     

槐定碱对心力衰竭大鼠心肌细胞钙诱导钙释放的影响

目的:研究槐定碱对心力衰竭大鼠心肌细胞钙诱导钙释放的影响。方法:结扎大鼠冠状动脉左前降支制备心力衰竭模型,随机分为假手术组、心力衰竭组、槐定碱5 mg/kg、10 mg/kg和20 mg/kg剂量组。4周后酶解法分离各组大鼠心室肌细胞,采用膜片钳和激光扫描共聚焦显微镜同步实时记录系统记录心肌细胞的L-型钙电流(ICa.L)及胞浆内的钙瞬变。结果:心力衰竭组大鼠心肌细胞的ICa.L、钙火花发生率及钙瞬变峰值明显低于假手术组;槐定碱中剂量和高剂量组大鼠心肌细胞的ICa.L、钙火花发生率及钙瞬变峰值明显高于心力衰竭组;槐定碱低剂量组与心力衰竭组相比差异不显著。结论:一定浓度的槐定碱对改善心力衰竭大鼠心肌细胞钙诱导钙释放功能具有重要的作用。     

Mechanisms of the origination of hypersegmented (hyperdiploid) neutrophils in rats as affected by cyclophosphamide

Feulgen cytophotometry has revealed tetraploid DNA content in some hypersegmented mature granulocytes in rat peripheral blood after two weeks of daily injections of cyclophosphamide (20 mg/kg of body weight). In bone marrow of rats which were given the preparation for 7 days myeloblasts, promyelocytes and myelocytes are blocked in G2 phase of the mitotic cycle. About 50% of metamyelocytes, bands and segmented granulocytes are also tetraploid. Thus cyclophosphamide has induced tetraploid hypersegmented neutrophils in rats as a result of maturation of G2 blocked proliferative pool granulocytes.     

Characteristics of the carcinogenic action of methyl(acetoxymethyl)nitrosamine and DNA repair in rats of different ages

A pattern of DNA methylation and carcinogenesis has been studied in young (3 month-old) and old (14 month-old) female rats following a single intravenous injection (13 mg/kg) of methyl(acetoxymethyl)nitrosamine (DMN-OAc). The incidence of various tumours as well as the incidence of tumours in some peculiar sites were found to be similar in young and old DMN-OAc-treated rats. The life time of old rats was less than that in young animals; the average period of tumour detection was also shorter in old rats. In both young and old animals the highest concentrations of methylated purines were found in lung and kidney DNA. However, the level of DNA methylation in old rats was higher than in corresponding tissues of young animals. Efficiency of O6-meG repair in methylated template DNA was found to be the highest in liver extracts of 1- and 12-month-old rats. Further, by the age of 2 years, the activity of O6-meGT decreased. The findings suggest that different age periods could be characterized by different efficiency of DNA alkylation, synthesis and repair.     

Prospects for using the cryogenic factor in the radiation therapy of tumors

Experimental studies with 640 mongrel male rats with transplants of Guerin carcinoma and DMBA-induced tumours were performed. Separate groups of animals were subjected to isolated effects of cryodestruction, radiation therapy with total doses of 60 or 30 Gy and combined cryoradiation treatment by different schedule. The study revealed that an enhanced efficiency of combined treatment is achieved essentially by a two-fold decrease in the total irradiation dose in combination with tumour focal cryodestruction.