7-Methylguanine Inhibits Colon Cancer Growth in Vivo.

7-Methylguanine (7-MG) is a natural inhibitor of poly(ADP-ribose) polymerase 1 and tRNA-guanine transglycosylase, the enzymatic activity of which is central for the proliferation of cancer cells. Recently, a number of preclinical tests have demonstrated the safety of 7-MG and a regimen of intragastric administration was established in mice. In the present work, the pharmacological activity of 7-MG was studied in BALB/c and BALB/c nude mice with transplanted tumors. It was found that 7-MG effectively penetrates tumor tissue and suppresses colon adenocarcinoma growth in the Akatol model, as well as in a xenograft model with human HCT116 cells.

[Inhibitory effect of human lactoferrin (neolactoferrin) on the growth of transplantable tumor in the uterine cervix of mice].

There was studied effect of recombinant form of human breast milk component-lactoferrin, received from milk of goats-producers (neolactoferrin), on growth of transplantable tumor of the cervix in mice (TTC-5). Neolactoferrin in dose of 100 mg/kg and 200 mg/kg of animals' mass inhibited the rate of tumor growth. The most effective was the dose of 200 mg/kg, which was entered a week before transplantation. In contrast to the control group, in groups where neolactoferrin was entered it was fixed resorption of TTC-5 in 6 mice. Repeated transplantation TTC-5 to these mice led to reducing of the rate of tumor growth and increasing of duration of their lives. To investigate if tumor-braking effect neolactoferrin connected with direct effect on the tumor or due to the general effect of the organism, TTC-5 cells were transformed in culture and they were exposed by neolactoferrin in dose of 10 and 100 mkg/ml. In investigated doses neolactoferrin did not influence on tumor cells growth. There is discussed possible mechanism of anti-tumor effect of neolactoferrin.

[The effect of preliminary administration of water with reduced deuterium content on the growth of transplantable tumors in mice].

It was investigated whether preliminary administration of water with reduced Deuterium content may modify the inhibitory effect of the water given to BDF1 and CDA mice on the day of tumor transplantation. Two models were used: Lewis lung carcinoma (LLC) and uterine cervical carcinoma (UCC). Experimental mice (20 per group) used the water with reduced Deuterium content. Water with a Deuterium content close to that of drinking water was given to controls (30 per group). Both kinds of water were given to mice 4 weeks before the experiment. Inhibitory effect was acknowledged by the time at which the first nodules appeared at site of transplantation and assessed with respect to volume of tumor and animal life-span. Metastasis inhibition coefficient was determined for Lewis carcinoma metastasizing to the lung. It was found that water with reduced Deuterium content effectively inhibited the growth of the transplantable tumors under study, significantly reduced metastasis weight in mice with LLC and increased life-span in animals with transplantable UCC.

[Low-deuterium water effect on transplantable tumors].

Such models of transplantable tumors as Lewis sarcoma, uterine sarcoma-322 and uterine carcinoma-5 were used to study possible inhibitory effect by low-deuterium water. Such water was given to experimental animals (20 mice in each group). Controls (30 in each group) received tap water with standard deuterium concentrations. Low-deuterium water treatment resulted in significant inhibitory effect on volume of all tumor patterns concerned: it delayed nodule formation at transplantation site. However, no increase in survival time was obtained.

[Consideration of the deuterium-free water supply to an expedition to Mars]. / Vozmozhnost' ispol'zovaniia bezdeiterievoi vosy v marsianskoi ékspeditsii.

Interplanetary missions, including to Mars, will put crews into severe radiation conditions. Search for methods of reducing the risk of radiation-induced cancer is of the top priority in preparation for the mission to Mars. One of the options is designing life support systems that will generate water with low content of the stable hydrogen isotope (deuterium) to be consumed by crewmembers. Preliminary investigations have shown that a decrease of the deuterium fraction by 65% does impart to water certain anti-cancer properties. Therefore, drinking deuterium-free water has the potential to reduce the risk of cancer consequent to the extreme radiation exposure of the Martian crew.

[Induction by benz(a)pyrene of squamous cell metaplasia of the respiratory epithelium in organ cultures: importance of the route of administration of the carcinogen and genetic susceptibility of the animals]. / Induktsiia benz(a)pirenom ploskokletochnoi metaplazii respiratornogo épiteliia v organnykh kulturakh: znachenie puti vvedeniia kantserogena i geneticheskoi chuvstvitel'nosti zhivotnykh.

A comparative study was made of transplacental (in vivo) and direct (in vitro) effects of benz(a)pyrene (BP) in the organ cultures of embryonal lungs of mouse susceptible (strain A) and resistant (C57 Bl) to pulmonary blastomogenesis. The development of the epithelium squamous cell metaplasia was observed only after direct application of BP on the lung explants in vitro. Correlation between metaplasia frequency and BP dose and duration of treatment and mouse susceptibility to pulmonary blastomogenesis is established. Thus, at all BP concentrations (3.6 or 12 micrograms/ml of medium) and maximum time of treatment (15 days) the frequency of squamous cell metaplasia in the lung explants of C57 B1 mice was very low (3.0, 2.0 and 4.2%, p > 0.1) while in a strain A it was significant at the doses of 6 and 12 micrograms/ml (10.4 and 23.4%, p < 0.001). No epithelial metaplasia developed when the time of BP treatment was decreased up to 7 days.

Perinatal lung carcinogenesis in mice: in vivo and in vitro correlation.

Perinatal lung carcinogenesis in susceptible (A) and resistant (C57B1/6J) to lung carcinogenesis mice was studied in (1) experiment in vivo and (2) in organ cultures of embryonic lung exposed to carcinogens directly (in vitro) or transplacentally (in utero): females were treated with carcinogens at 17-19 days of pregnancy, killed 1-2 days after the treatment and embryonic lungs were explanted in organ cultures. Transplacental and direct (in vitro) treatment with urethane and benz(a)pyrene (BP) induced in the explants: (1) stimulation of epithelial and mesenchymal cell proliferation; (2) increase of viability and survival as compared to the non-treated explants (growth stimulating effect); (3) morphological lesions (hyperplasia and squamous-cell metaplasia of epithelium, adenomatous growth and adenoma-like structures). All the alterations developed in treated lung explants depended both on host factors and carcinogenic treatment (type of carcinogen, dose, method of exposure, and duration of cultivation).

[Benzo(a)pyrene induces planocellular metaplasia of the respiratory epithelium in explants of embryonic mouse lung]. / Benz(a)piren indutsiruet ploskokletochnuiu metaplaziiu respiratornogo épiteliia v éksplantatakh émbrional'nykh legkikh myshei.

The direct effect of benz(a)pyrene (BP) induces squamous epithelial metaplasia (SEM) in organ cultures from embryonic lungs of C57BL and A. The incidence of SEM depend on the doses of BP (3-6-12 mkg/ml), duration of treatment and on the mice line.

[The dose-effect of benz(a)pyrene in organ cultures of embryonic mouse lungs resistant and predisposed to pulmonary blastomogenesis]. / Doza-éffekt benz(a)pirena v organnykh kul'turakh émbrional'nykh legkikh myshei, ustoichivykh i predraspolozhennykh k blastomogenezu legkikh.

A direct effect of benz(a)pyrene (BP) was studied on organ cultures from embryonic lungs of C57Bl and A mice. The toxic effect of 3, 6, 12 micrograms/ml BP was observed in alveolar epithelium and mesenchymal cells after 7 days of cultivation. After 14-21 days diffuse and focal hyperplasia of the epithelium was discovered in 35.5, 20.0 and 36.1% of treated cultures (explants) from embryonic lungs of C57Bl mice and in 45.5, 56.3 and 53.2% of treated explants from embryonic lungs of A mice. Squamous epithelial metaplasia was observed in 3.0, 2.2 and 4.2% of treated explants from C57Bl mice and in 2.4, 10.4 and 23.4% of treated explants from A mice. Total papillary adenomatous growth of the epithelium was discovered in 10.0, 18.3 and 36.1% of treated explants from embryonic lungs of A mice only. Thus, a direct effect of BP on organ cultures from embryonic lungs of C57B1 and A mice depended on BP doses and the mouse line.

[Sensitivity to benzo(a)pyrene of epithelial and mesenchymal cells of embryonic lungs of mice susceptible (line A) and resistant (line C57BL) to lung blastomogenesis]. / Chuvstvitel'nost' k benz(a)pirenu kletok épiteliia i mezenkhimy émbrional'nykh legkikh myshei, predraspolozhennykh (liniia A) i ustoichivykh (liniia C57BL) k blastomogenezu legkikh.

Proliferative activity of alveolar (EA) and bronchial (EB) epithelial cells, mesenchymal cells of explants (ME) and mesenchymal cells migrated on the cellulose filter (MF) was studied autoradiographically in the normal cultures and after treatment with benz(a)pyrene (BP). Labeling index (LI) of cells from the treated explants was higher or lower than in normal cultures, or did not differ from normal values. The effect of the treatment depended on BP dose, mouse strain, and the type of cells. Epithelial cells, especially EB, and ME cells from embryonic lungs of A mice were very sensitive to growth-stimulating effect of BP. In treated cultures from C57BL mice LI increased only in EB cells, however, unlike A mice, the effect inversely correlated with BP doses. Proliferative activity of EA, ME and MF cells was lower than in untreated explants from C57BL, the effect of treatment increasing with higher BP doses. The importance of local cell-tissue factors, namely epithelial-mesenchymal interactions, and the role of lung mesenchyma in the realization of genetically determined sensitivity to spontaneous and induced lung blastomogenesis in C57BL and A mice are discussed.