Antitumor and antimetastatic properties of N-methyl formamide--an agent related to differentiation of tumoral cells and unithiol, official detoxicating drug containing SH-groups were studied in C57Bl/6 mice inoculated with Lewis's lung carcinoma. The drugs were administered intraperitoneally into animals at days 1, 4, 7, 13 and 16 after carcinoma inoculation and their effects were evaluated at day 19. Single administration of unithiol, 5 mg/kg body weight, did not affect tumor growth and metastases spreading. At the same time, N-methyl formamide (single administration of 300 mg/kg body weight) inhibited tumor growth and decreased 5-fold an amount of spontaneous metastases in lungs. However, the antitumor and antimetastatic activities of N-methyl formamide were decreased after simultaneous administration with unithiol. Importance of SH-groups in therapeutic effects of N-methyl formamide is discussed.

The cancerogenic activity of the dispirotripiperasinium derivatives prospidine and spirobromine was tested in concurrent use with sodium nitrite. The drugs were intragastrically administered once a week. It was combined with sodium nitrite, 35 mg/kg, to non-inbred rats of both sex during 24 months. A morphological study revealed no statistically significant reduction of latency and no increase in the incidence of tumors in laboratory animals. No cancerogenic effect of sodium nitrite was found.

The authors examined the interaction of 1,2-benzoquinone derivatives with HeLa cell cultures and ascite Ehrlich's cancer cells. 4-N (anilino)-5-methoxy-1,2-benzoquinone was found to produce a marked toxic effects against tumor cells. The cytotoxic effect is oxygen dependent and associated with the formation of oxygen radicals in quinone's redox cyclization reactions. The inhibitory analysis was used to show that the major mediators of the toxic action of the agent are superoxide radical-anion and hydrogen peroxide. It is concluded that the interaction of highly toxic oxygen radicals, which are generated in quinone redox cyclization, with plasma membrane cells is likely to be the mechanism responsible for cellular destruction when quinones act on tumor cells.

The authors studied the degree of DNA damage in in vitro cultured human peripheral lymphocytes (PL) and Jurcat's human T-cell lymphoma cells exposed to a stabilized 4 OH-cyclophosphan-mamophosphatide (MA) derivative, as well as in the leukocytes from patients with leukemia who were treated with cyclophosphan. There was an increase in alkaline DNA denaturation rate of LP lysates and T-cell lymphoma cells, which was in proportion to MA concentrations, and a higher sensitivity of LP to the genotoxic effect of MA given in doses of 5-10 micrograms/ml than that of Jurcat's cells, as well as high peripheral lymphocyte and neutrophil DNA damages in patients with leukemia during chemotherapy. The authors consider that the accumulation of single-strand breaks and alkaline-labile sites, which was recorded from the increase in alkaline DNA denaturation rate of cell lysates, is a highly sensitive test for detecting DNA damages in resting and slowly proliferating cells and can be useful in revealing and evaluating the severity of human genotoxic effects.

The problems of anticarcinogenesis are discussed in the context of mechanistic approaches and the well-known mechanisms of multistage carcinogenesis. Various events at extra- and intracellular levels are involved in mutagenesis and carcinogenesis. The most promising candidates for suppression of chemical carcinogenesis are some nitrosation modifiers, dietary sorbents, metabolic activation modulators, reactive metabolite trappers, repair inducers, gene expression inhibitors, etc. Short-term tests for mutagenicity are more preferable for screening potential anticarcinogenic agents. The bioassays for anticarcinogenesis should be assessed for sensitivity, specificity and predictability and the genetic profiles of the antimutagenic activity of the modifiers analysed.

The mutagenic activity of some antitumor agents and the antituberculous agent isoniazid was studied by using some methods for estimating mutations on the Drosophila, mammals, and human cells. It was shown that mutagenic effects could be modified by adding various auxiliaries to the formulations of the drugs. The mechanisms of modifications were examined by pharmacokinetic techniques.

The literature data involving 45 references are reviewed. Metabolism of carotenoids in human and animal tissues, distribution in tissues, antioxidative and immunomodulating activities of carotenoids, their anticarcinogenic properties are discussed. Use of remedial drugs containing beta-carotene holds much promise.

Cefoperazone is a semisynthetic cephalosporin of the 3rd generation (cefobid, Pfizer, USA). It was used in monotherapy of 12 oncological patients during ++post-cytostatic aplasia of the bone marrow and peripheral pancytopenia after bone marrow transplantation. The results were favourable in 67 per cent of the patients: the body temperature normalized and no signs of any infection were evident. In 25 per cent of the patients the monotherapy failed and it was necessary to combine cefoperazone with aminoglycosides. Therefore, cefoperazone proved to be an efficient antibacterial drug, whose use was possible in the monotherapy of oncological patients after transplantation of the bone marrow.

Intravesical chemotherapy (IVC) for bladder cancer was conducted in 83 patients who had been admitted to the Moscow Cancer Research Center in 1981-1988. Farmorubicin IVC produced a complete response (CR) in 3 (21.4%) and a partial one (PR) in 6 (42.9%) of the 14 patients treated. In mytomicin C administration CR was achieved in 4 (30.8%), PR in 2 (15.4%) of the cases. For adriamycin, spirobromin, thiotef (60 mg), thiotef (20 mg), CR was registered in 4 (30.8%), 5 (17.9%), 1 (11.1%), 2 (18.2%), 2 (25%) patients, PR in 2 (15.4%), 8 (28.6%), 1, 1 (9.1%), 1 (12.5%) patients out of 13, 28, 9, 11, 8 cases, respectively. Complications of the IVC in the form of drug cystitis occurred in 57.1%, 23.1%, 46.4%, 12.5-18.1% of those treated with farmorubicin, mytomicin C, adriamycin, thiotef, respectively. Spirobromin arose no complications.

El-4 and P-815 murine tumor cells labelled by 125I-deoxyuridine or 51Cr were administered in 7-day subcutaneous syngeneic tumors or subcutaneously. At the same time different groups of mice were treated by LPS plus MDP, beta-C7H15-MDP, dexal-MDP, polyacrylamide-MDP-phosphatidylethanolamine, adriblastin or cyclophosphamide. It was shown that cytostatics and immunomodulators significantly delayed catabolism and withdrawing of 125I-deoxyuridine (that has not been incorporated in DNA) from tumor cells. This delay was correlated with the inhibition of tumor nodes growth rate. It is concluded that influence of cytostatics and immunomodulators on catabolism and withdrawing rate of 125I-deoxyuridine from tumor cells relates to their cytostatic effect and may be used at the earliest screening step of immunomodulator analysis.

Cytotoxicity of strophanthin G and digoxin was studied in experiments on lymphoid cells and carcinoma of cervix uteri cells. The glycosides inhibited the growth of three strains of cultured tumor cells tested. It has been found that highly toxic doses of the drugs produced no changes in the cell multiplication of normal human fibroblasts.

The cytogenetic effects of antitumor drugs with different action mechanism on the genetic structure of bone marrow hemopoietic cells were studied in experiments on CBA mice. It has been shown that single injections of doxorubicin (6 mg/kg), vinblastin (2.2 mg/kg), cyclophosphamide (250 mg/kg) and continuous administration of doxorubicin (0.95 mg/kg), vinblastin (0.24 mg/kg), cyclophosphamide (27 mg/kg) in 1/10 LD50 x 10 induce the formation of bone marrow cells with cytogenetic damage and peripheral red blood cells with micronuclei. The cytogenetic damage of hemopoietic tissue may be detectable 1-3 months after cytostatic influence.

We studied the condition of CBA mice bone marrow hemopoiesis and functional activity of adherent cells 6 months after a single treatment with vinblastine (VB), doxorubicin (DR) and cyclophosphamide (CP) in LD10 dose (6, 22 and 250 mg/kg, respectively). There was a long-term disorganization of bone marrow cell composition. The damage may be attributed to exhaustion of the pools of stem cells and changes in function of the cells formed by hemopoiesis induction microenvironment.

The present review (for the previous part, see Bioorganicheskaya Khimia. 1990. V. 16. No 11. P. 1445-1464) describes the most important studies in the chemical modifications of the sugar moiety of anthracycline antibiotics and their analogues during last ten years.

Based on literature data on effects of various preparations on the glycolysis in tumor and normal cells, a glycolytic molecular biochemical marker is proposed to screen chemical substances as potential antitumor drugs. A glycolytic specificity was noted in tumor cells which was regarded as a criterion for distinction of tumor cells from normal ones and among various histotypes of tumor cells as well as for the selective sensitivity of tumor cells to a substance. 17 of 38 substances tested were observed to inhibit glycolysis in tumor cells. The testing chemical substances for an antitumor activity with application of the glycolytic marker is recommended. A possibility is discussed of applying the marker for testing potential antitumor drugs, their individualization, and genetic typing.

Thermal properties of chromatin in cell composition of BALB/c mice and whole chromatin at injection of cis-Pt(CuO)2(CuOH)2 to experimental animals were studied by high sensitive DSM assigning for investigating complex biological systems. It is established that injection of cis-Pt(CuO)2(CuOH)2 to leukemic mice in vivo changes the thermal characteristics of spleen cells, so that they look like the thermal properties of the healthy mice spleen cells. It was supposed that small doses of Pt(CuO)2(CuOH)2 in the case of leukemia show anticarcinogenic properties and the overdoses promote malignization; in the norm at any concentration of the injected salt cancerogenic properties are exhibited.