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Motor neuron disease (MND), or amyotrophic lateral sclerosis, is a fatal neurodegenerative disorder characterized by a progressive loss of motor neurons in the spinal cord and the brain. Several angiogenic and neurogenic growth factors, such as the vascular endothelial growth factor (VEGF), angiogenin (ANG), insulin-like growth factor (IGF) and others, have been shown to promote survival of the spinal motor neurons during ischemia. We constructed recombinant vectors using human adenovirus 5 (Ad5) carrying the VEGF, ANG or IGF genes under the control of the cytomegalovirus promoter. As a model for MND, we employed a transgenic mice strain, B6SJL-Tg (SOD1*G93A)d11 Gur/J that develops a progressive degeneration of the spinal motor neurons caused by the expression of a mutated Cu/Zn superoxide dismutase gene SOD1. Delivery of the therapeutic genes to the spinal motor neurons was done using the effect of the retrograde axonal transport after multiple injections of the Ad5-VEGF, Ad5-ANG and Ad5-IGF vectors and their combinations into the limbs and back muscles of the SOD1(G93A) mice. Viral transgene expression in the spinal cord motor neurons was confirmed by immunocytochemistry and RT-RCR. We assessed the neurological status, motor activity and lifespan of experimental and control animal groups. We discovered that SOD1(G93A) mice injected with the Ad5-VEGF + Ad5-ANG combination showed a 2-3 week delay in manifestation of the disease, higher motor activity at the advanced stages of the disease, and at least a 10% increase in the lifespan compared to the control and other experimental groups. These results support the safety and therapeutic efficacy of the tested recombinant treatment. We propose that the developed experimental MND treatment based on viral delivery of VEGF + ANG can be used as a basis for gene therapy drug development and testing in the preclinical and clinical trials of the MND.

Study microbicidal activity of low temperature argon plasma (LTP) that is a stream of partially ionized argon having macroscopic temperature of the environment against Chlamydia trachomatis obligate intracellular parasites. Study viability of host cells in parallel.McCoy line cells infected with C. trachomatis (Bu-434/L2 strain) were exposed to LTP obtained by using atmospheric pressure plasma SHF generator. Intracellular localization of chlamydiae was visualized by luminescent microscopy.Exposure of infected McCoy line cells resulted in the destruction of chlamydia inclusions and practically complete elimination of intracellular bacteria. At the same time LTP exposure did not result in immediate death of host cells, an insignificant reduction of the number of cells was observed 24 hours after the exposure to LTP.The effect of LTP for elimination of intracellular chlamydia without significant changes in viability of eukaryotic host cells was demonstrated.

Pattern-recognizing receptors (PRR) play a key role in the functioning of human immune system. They are the primary sensors of infection capable of distinguishing between various highly conservative molecular patterns (pathogen-associated molecular patterns (PAMPs)) contained in pathogenic organisms. Binding of these molecular patterns to PRR induces a variety of reactions of innate (secretion of proinflammatory cytokines and antimicrobial peptides, activation of phagocytosis, etc.) and adaptive (antibody processing and presentation, polarization of T-cell response, etc.) immunity. Great interest in the molecular mechanisms of pathogen recognition resulted in the discovery of numerous PRR. The aim of this review is to systematize the currently available data on PRR, their specificity, and role in the formation of anti-inflammatory immunity.

A murine model of incisional wound was used to evaluate effect of topical application of purified bacterial lipopolysaccharide on the wound healing process. Thirty five ICR mice were used in the study. It was shown that bacterial lipopolysaccharide is a strong promotor of wound healing. It increases tensile strength, accelerates completion of the inflammatory process, stimulates collagen deposition and early remodeling.

High frequency of epidemiological threats (H5N1 influenza, SARS, etc.) in modern world calls for the development of new flexible technologies for manufacturing efficacious vaccines and rapid reorientation of their production as appropriate. Genetic vaccination is one of such technologies aimed at prophylaxis of dangerous and socially significant infections. The technology is based on administration of one or several functionally active genes encoding for antigens of pathogens which induces formation of both cellular and humoral immunity against the respective microorganism. This property of genetic vaccines is used for the development of prophylactic schemes. New vaccines are currently being designed to prevent a variety of infections. The aim of the present review is to outline major trends in genetic vaccination leading to the improvement of its efficacy.

Results of application of LTP at atmospheric pressure as an antibacterial agent during the last decade are considered with reference to physicochemical mechanisms of its bactericidal action. The principles of designing modern LTP sources are described in conjunction with the results of LTP application against pathogenic bacteria in vitro and in biofilms. The possibility to destroy biofilm matrix by LTP is estimated along with the results of its testing for the treatment of acute and chronic wound surfaces. Prospects for the development of "plasma medicine" in this country and abroad are discussed with special emphasis on its advantages, such as the absence of long-acting toxic compounds, small probability of spontaneous mutations accounting for resistance to LTP, relatively low cost of LTP sources, independence of LTP effect of the surface relief, painless application.

Comparative antimicrobial activity of lactoferrins from various sources (native lactoferrin from Laprot, human hololactoferrin, recombinant human lactoferrin isolated from the cultural medium of permissive cell culture transfected using pseudoadenovirus nanostructure with the human lactoferrin gene, and native bovine lactoferrin) was studied to prove the possibility of their use for development of antimicrobial drugs. It was shown that all the substances were active against the Bacillus standard strains. The antibacterial activity was almost independent of the degree of saturation the lactoferrin molecules with Fe3+. The native human lactoferrin was more active than hololactoferrin against Candida when evaluated by the minimum inhibitory concentration (MIC). Fe(3+)-Non aturated recombinant human lactoferrin demonstrated the antimicrobial activity (by MIC) similar to that of the native human lactoferrin. The results showed that native and recombinant human lactoferrins might be used for the development of intravenous and intracavitary dosage forms, while the native bovine lactoferrin could be useful in development of oral drugs.

To design and study the properties of candidate vaccines against avian influenza based on recombinant adenoviral vectors expressing H5 hemagglutinin.Recombinant adenoviral vectors were constructed as described in "Stratagene" (Ad Easy Adenoviral Vector System). For immunization of animals, recombinant candidate vaccines were administered intranasally twice. Titer of hemagglutinating antibodies were measured by hemaglutination inhibition assay.It was demonstrated that administration of vaccines to animals completely protects them from a lethal dose challenge with H5N2 influenza virus. Protective effect of vaccines remained for 6 months after immunization. Additionally, highly effective cross-protection of the immunized animals against heterologous strain of H5 influenza virus was demonstrated.Obtained results show good prospects for usage of recombinant adenoviral vectors as a basis for development of new generation effective vaccines against influenza.

The thanatogenetic mechanisms of stem cells (SC) of rapidly renewing system of intestinal epithelium still remain unclear. On the one hand, they are definitely involved into basic mechanisms of carcinogenesis in the gastrointestinal tract, because dysregulation of programs responsible for elimination of "unwanted" mutant cells (which are normally under immune and own intrinsic control) is one of the reasons of neoplastic expansion. On the other hand, elucidation and characterization of the regulatory machinery controlling SC survival are interrelated with problems of clinical medicine, including the increase of therapeutic efficiency of treatment of inflammatory and ulcer lesions of the gut, traumatic and surgical wounds, as well as restriction of side effects in normal tissues induced by application of intensive methods chemo- and radiotherapy of cancer. The latter is especially important for treatment of blood diseases and tumors of peritoneal cavity organs mainly due to bone marrow and intestinal epithelium damage. (These tissues are the most sensitive to these treatments.) The review considers data on exogenous and genetic modifiers of SC survival, and also the basic principles of mechanisms involved into renewal and regeneration of SC and the effects of microbiota on these processes.

Various strains of mycoplasmas cause activation of transcriptional factor NF-kB as a result of interaction with different combinations of Toll-like receptors (TLR). It is well known that the MALP-2 protein of M. fermentans activates the NF-kB through interaction with the TLR2/6, lipid-associated membrane lipopeptides (LAMPs) of M. penetrans through the TLR1/2, LAMPs of M. pneumoniae through combinations of Toll-like receptors (TLR2/6 and TLR1/2), and superantigene of M. arthritidis through the TLR2 and TLR4-dependent pathways. In this study, we defined specific Toll-like receptors for LAMPs of M. arginini. For carrying out the research we used cell lines 293-null, 293-hTLR2, 293-hTLR1/2, 293-hTLR2/CD14, 293-hTLR2/6, 293-hTLR4/ CD14-MD2 expressing certain combinations of TLR and their coreceptors. It was shown that LAMPs of M. arginini cause activation of NF-kB interacting with TLR2/1, TLR2/6 and TLR2/ CD14, but not with TLR2 alone or TLR4.

Aviadenovirus CELO is a promising vector for gene delivery to eukaryotic cells, including mammalian cells. In the present state of affairs, it gives a chance to apply recombinant adenoviruses CELO against animal pathogens. High expression level of transgene consisting of virus vector is necessary to reach protective humoral and T-cell immune answer. One of the approaches to enhance the expression level of transgene consisting of viral vectors is inclusion of addition 5'- and 3'- untranslated regulatory elements (PARS, IRES, WPRE) to the expression cassette. In this work, 5'-untranslated regulatory elements of major late transcription unit of CELO genome (a bipartite leader and gene hexon leader) were used for construction of the expression cassette consisting of the recombinant adenovirus CELO to provide high expression level of reporter gene of secreted alkaline phosphatase in nonpermissive cell system. It was shown in our experiments that the obtained recombinant adenovirus CELO was characterized by enhanced (2.4-3.5 times) expression level of reporter gene in transduced mammalian cells in vitro and in vivo.

NF-kappaB is one of the main transcriptional factors that is responsible for cell survival under stresses. It was shown that various species of mycoplasma and their structural components were able to stimulate NF-kappaB activation as a result of their interaction with specific toll-like receptors on eukaryotic cell surface. Based on these studies, we suggested that activation of NF-kappaB in response to mycoplasmal infection could enhance the resistance of infected cells in response to proapoptotic stimuli. In this study we showed that infection of cells expressing toll-like receptors TLR2/6 with mycoplasma M. arginini leaded to suppression of apoptosis induced by chemotherapeutic agents (cisplatin, 5-fluorouracil, taxol).

The avian recombinant adenovirus of serotype 1 (CELO) was obtained. The recombinant adenovirus of serotype 1 (CELO) induces expression of human beta-interferon (IB). The expression cassette containing IB gene was placed at the right end of the CELO genome under control of hybrid promoter hEF-1alpha/HTLV. The resulting recombinant adenovirus CELO-IB transduced the avian cell culture LMH. The level of production of the recombinant IB was 0.15 micro/ml. The IB protein yield after affine chromatography purification using Ni-NTA agarose was 50%. The biological activity of the purified IB was high (7.8 x 10(8) MU/microg protein). The purified IB inhibited replication of murine encephalomyocarditis virus (VMEC) in cell culture of human diploid fibroblasts (HDF). Thus, expression system based on avian cell culture is an effective system for producing biologically active protein of human interferon beta.

Recombinant avian adenovirus CELO bearing sequence RGD in the structure of a HI-loop of long fiber was designed. Experiments in vitro revealed that introduction of RGD-motif into fiber of CELO increased the ability of the virus to be attached to a surface of CAR-negative cells, and raised efficiency of the process of internalization of the virus both in CAR-positive, and in CAR-negative cells.

The article contains experimental data on angiogenesis stimulated by plasmid containing the angiogenin gene. After the introduction of the gene construction, the number of capillars in the chorion-allantois membrane increases 2 to 3 times; in an ischemized limb of a rat it increases by 20 to 30%. Intramuscular administration of genetic engineering construction to patients with chronic lower limb ischemia improved the patients' condition, consisting in an increase in painless walking distance and ankle-brachial index, as well as in trophic defect healing and the betterment of muscular perfusion. Positive effects were noted after 2 to 4 weeks of treatment and remained during 6 to 24 months. There were no side-effects, except low grade fever during 1 to 2 days.

A highly purified TUL4-CBD chimeric protein was obtained by one stage purification method. TUL4-CBD protein consists of TUL4 Francisella tularensis mature peptide sequence, Gly-Ser spacer and cellulose binding domain (CBD) of Anaerocellum thermophilum. The TUL4-CBD protein was shown to induce production of specific antibodies to TUL4 protein in laboratory animals.

Vaccination with DNA-vaccines is a new approach in immunization that implies application of genetic constructions coding certain proteins of various pathogens instead of conventional ways of vaccination with inactivated or attenuated microorganisms. The main advantage of this approach consists in possibility to induce immune response in cases when the disease cannot be prevented by routinely used prophylactic vaccines. This advantage is attributed to the ability of DNA-vaccines to focus immune response (cellular, humoral or both) upon one or several certain pathogenic antigens, which is impossible in principle when conventional vaccines are used and does not occur during an infectious process. The efficiency of DNA-vaccines is currently being tested in various pre-clinical and clinical trials. Genetic vaccination has induced protective or therapeutic immune response in a significant number of these trials. However, despite numerous positive results, clinical use of DNA-vaccines has not been recommended yet.

The CELO recombinant avian adenovirus carrying the gene coding the human angiogenine (ANG) synthesis was obtained. Expression of the angiogenine gene was shown in the LMH cell culture after infection with the CELO-ANG virus. The ability of CELO recombinant adenoviruses to carry out the delivery and expression of alien genes in muscle cells was demonstrated in experiments with laboratory animals (Wistar line rats). The induced neovascularization in rat muscles after the animals were administered the CELO-ANG viruses was shown.

The review contains information on modern approaches to the development of antituberculosis vaccines and remedies. Data on the comparative effectiveness of different subunit and DNA vaccines against tuberculosis are presented. The use of comparative and structural genomics for the search and characterization of new Mycobacterium tuberculosis genes, whose products may prove to be important antigens for the development of vaccines or target proteins for remedies against tuberculosis, is considered.

A method was elaborated to evaluate the biological activity of expression products of gene in the plasmid vectors, which are crucial for the synthesis of growth factor of blood vessels. It was proven as possible that the chrioallantonic membrane (CAM) of chicken's embryos could be transfected by recombinant plasmids containing both the reporter and target genes. The efficiency of CAM transfection was assessed by a plasmid carrying the reporter gene of green fluorescent protein (GFP). Finally, it was demonstrated that, at an infiltration of the recombinant plasmid containing the human angiogenine gene, its expression products induce the neovascularization in the CAM cells of chicken's embryos and stimulate an accretion in vessels of the 1st, 2nd and 3d orders.

Recombinant adenoviruses capable of expressing the gene of secreted placentary alkaline phosphatase (SEAP) under control of CMV-promoter was obtained on the basis of CELO avian adenovirus and human adenovirus-5 (Ad5) genomes. The efficiency of the CELO vector was determined in experiments with transduction of human (293, A549, and H1299), mouse (B16), and avian (LMH) cell cultures. It was shown in C57BL/6 mice in vivo that SEAP gene is expressed under conditions of intravenous, intranasal, and intratumoral application of recombinant adenovirus CELO-SEAP. The duration of expression of the alkaline phosphatase CELO = SEAP gene in immunocompetent mouse body was 21 days. The level of SEAP gene expression was measured in the allantois fluid of chicken embryo infected with recombinant adenovirus CELO-SEAP.

Recombinant CELO avian adenoviruses carrying green fluorescent protein (GFP) and and human interleukin-2 (IL-2) genes were obtained by homologous recombination in cell culture. The resultant recombinant CELO viruses are reproduced in chick embryos in the renal tubular and chorionic allantoic membrane cells. The ability of CELO vectors to transduce human and animal cells was studied in vitro (in cell cultures) and in vivo (in laboratory animals). GFP gene delivery and expression in recombinant CELO virus in tumors in C57BL/6 mice were for the first time demonstrated for B16 melanoma. Human IL-2 gene expression and protein accumulation in allantoic fluid of chick embryos infected with CELO-IL-2 vector were detected for the first time.

Transcription of E1b region of avian CELO and EDS adenoviruses was investigated in infection of primary chicken kidney cell culture with these viruses. Transcription of Gam-1 gene of CELO virus and predicted large T antigen of EDS virus was observed 4 and 24 h after cell infection.

The nucleotide sequence of a part of the HindIII-D fragment (3300 b.p.) of adenovirus KR95 DNA has been determined. Analysis of the nucleotide sequence disclosed a continuous ORF for hexon gene (2814 b.p.) coding the 937 residue protein, part of ORF for the C-terminal region of pVI polypeptide, including 114 residues and the beginning of ORF coding 25 N-terminal residues for viral endoproteinase. Comparison of predicted KR95 hexon sequence and 8 mammalian and avian adenovirus hexon sequences revealed the highest homology between KR95 strain and avian adenoviruses FAV10 and FAV1 (91.1 and 80.1%, respectively). The results were used for creating a test system on the basis of the polymerase chain reaction. The system was used in analysis of fowl samples obtained from 12 poultry farms in Russia. The sequences of hexon gene amplified fragments in the isolated strains and similar fragments of other mammalian and avian adenoviruses have been compared.

The cores of egg-drop syndrome virus (EDS-76) were isolated by the pyridine technique. EDS-76 proved to be much more resistant to pyridine disruption than other adenoviruses and treatment with 10% pyridine did not lead to complete dissociation of capsid and cores; only increase of pyridine concentration to 20% produced satisfactory results. At least three polypeptides (24, 10.5, and 6.5 kDa) were found in the core by SDS-PAGE, whereas the 40 kDa reacting with the core is most probably not a core component. Much more intensive reactions of the core with EDS-76 virion capsid suggest that its virion structure differs from that of other adenoviruses.

A nondefective recombinant human adenovirus 5 (Ad5) carrying the gene encoding for the porcine rotavirus outer capsid protein VP7 in the E3 region of the Ad5 genome has been obtained. mRNA for VP7 in recombinant Ad5KV14/VP7 infected cells was demonstrated by means of RT-PCR. Radioimmunoprecipitation of cell extracts infected with Ad5KV14/VP7 on early (12 h p.i.) and late (24 h p.i.) stages of adenovirus infection with rabbit polyclonal antiserum raised to purified rotavirus virions revealed a recombinant protein possessing the same electrophoretic mobility, 37 kDa, as the native rotavirus K VP7. One-dimensional peptide mapping also demonstrated the identity of the recombinant and native VP7.

A ribozyme was constructed of the catalytic domain of tobacco ringspot virus satellite RNA and flanking sequences complementary to the target, secreted alkaline phosphatase (SEAP) mRNA. The ribozyme specifically cleaved the substrate in vitro; compared with that constant temperature. The relationship between specific endoribonuclease activity of the ribozyme and Mg2+ concentration was shown. The ribozyme was active in 293 cell line which was cotransfected with plasmids carrying the SEAP gene under control of RSV LTR promoter and the ribozyme gene under early HCMV promoter: SEAP activity reduced by half.

The envelope proteins of chicken infectious laryngotracheitis virus were investigated using immunoblotting, radioimmuno-precipitation, and diagonal SDS-PAGE. Polypeptides with molecular weights of 205, 155, 115, 90, and 60 kDa were detected by rabbit antiserum and those of 205, 115, 90, and 60 kDa by chicken antiserum. When chicken antiserum was used, the 60 kDa polypeptide appeared to be the major immunogen. The 60 kDa polypeptide was shown to be a disulfide linked dimer with a molecular weight of 112 kDa. It is suggested that 60 kDa polypeptide is present in virions both in dimer (112 kDa) and monomer (60 kDa) forms.

DNAs extracted from the RAT2 cells transformed by the CELO virus (strain Phelps) have been analyzed by polymerase chain reaction. Sequences belonging to the left end of the viral genome (according to IshibashiYasue, 1984) were not found in the tested DNAs. On the other hand, the polymerase chain reaction data have revealed the presence of fragments specific of the opposite end. We conclude that this region may have included the genes responsible for cell transformation, at least as far as Phelps viral strain is concerned.

The plasmid pH5KV14 containing the right end of the Ad5 viral genome (45-100 map units) with deleted nonessential E3 region (78.5-84 map units) has been constructed. A helper-independent recombinant virus Ad5KV14 has been obtained as a result of in vivo transformation of the line 293 human cells by the pH5KV14 plasmid DNA and an EcoRI-A DNA fragment of the virus Ad5 and subsequent recombination. A nondefective recombinant virus Ad5KV17 containing the Ad5 genome with the E3 region substituted for the plasmid DNA fragment coding for the kanamycin-resistance has been constructed by a similar procedure.

The nucleotide sequence of 92-100% of the adenovirus CELO (FAV1), strain Phelps, genome has been determined. The computer analysis of the sequences revealed a ClaI site methylated by m*Ecodam. A recognition site for XbaI and two sites for PstI, not found in the corresponding genome of CELO, strain Ote, have been determined. Three extensive (more than 100 amino acid residues) open reading frames exist, coding for the polypeptides with molecular weights of 31.5, 19.3 and 14.5 kD (276, 178 and 128 amino acids, respectively). Some shorter open reading frames have been detected as well within the sequences studied.

This review is devoted to the molecular and biological properties of natural and artificial Ad-SV40 hybrids. The conditions of adenovirus and SV40 recombinant formations are discussed. The principal one is the ability of the C-terminal portion of the SV40 T-antigen to carry a helper function for growing human adenoviruses in the cultures of simian cells, in which the adenoviruses themselves are not reproduced. The data about the structural and functional organization of the hybrid RNA and proteins, tumor properties of defective and nondefective Ad-SV40 recombinants are provided. A special chapter is devoted to the construction of Ad-SV40 hybrids in vitro. The possibility of using them not only for the investigation of adenoviral properties, but for the super production of different proteins is marked. Alongside the corresponding region of SV40 genome may perform the function of a selection marker for the creation of eucaryotic vectors on the basis of adenoviruses.

The effect of restricting endonucleases Eco R I, BgI II and Sal I on simian adenovirus type 38 (SV-38) DNA was studied. Bgl II restrictase cleaves the virus DNA into 4 fragments, A, B, G, and D, with molecular weights 9.3 x 10(6), 3.3 x 10(6), and 2.9 x 10(6) daltons, respectively. After restriction with Eco R I and Sal I SV-38 DNA cleaves into 5 and 6 fragments, respectively. The molecular weights of Eco R I fragments are A--8.2 x 10(6), B--6.5 x 10(6), C--4.0 x 10(6), D--1.27 x 10(6), and of Sal I fragments: A--6.5 x 10(6), B--5.4 x 10(6), C--4.2 x 10(6), D--2.8 x 10(6), E--2.5 x 10(6), and F--0.25 x 10(6). By restriction of DNA-protein compex by means of partial DNA hydrolysis, combined Bgl II and Eco R I hydrolysis and secondary restriction of a fragment eluted from the agar gel, the alternation of Eco R I and Bgl II fragments in SV-38 genome was determined.

A comparative analysis of hexons of human adenovirus (HAdV) types 1, 2, 6 and simian adenovirus type 7 (SA7) was carried out by peptide mapping. Common and unique peptides were found in hexons from virions of human adenovirus types 2 and 6 and SA7. The similarity of hexons of HAdV types 2 and 6 was shown to be more marked than HAdV and SA7 hexons. Similar data were obtained in the analysis of excessively synthesized (soluble) hexons of HAdV types 1 and 6 and SA7. A significant homology between structural and soluble hexons of HAdV-6 HAdV-6 was established, and several peptides unique for each of them were discovered. The significance of the experimental results is discussed.

Optimal conditions for ligation of simian adenovirus type 7 (SA-7) DNA fragments formed under the effect of treatment of the intact molecule with Eco RI endonuclease were established. It was shown that up to 30% of the original material may be ligated and transferred into a structure with molecular weight 23 X 10(6) daltons which corresponded to the molecular weight of the intact SA-7 DNA. The data of the existence of one recognition site for Eco RI in SA-7 DNA were confirmed. The biological activity of the ligated material was demonstrated on lambda-III phage DNA.

The transforming and oncogenous activity of uncleaved DNA of simian adenovirus SA7 (AdSA7) and the products of its restriction by endonucleases R. Bam HI and R. SalI was studied. It was shown that uncleaved virus DNA transformed the rat kidney cells and rat embryo fibroblasts and induced tumors in newborn hamsters. AdSA7 DNA, hydrolysed by R. Bam HI, posessed the transforming activity. The mixture of DNA fragments, obtained after hydrolysis by R. SalI was oncogenous in hamsters.

The highly active preparations of specific endonucleases Eco RI and Bgl II were purified by affinity chromatography from E. coli and Bacillus globiggii cells, respectively. The isolation and purification procedures included cell disruption by ultrasonication, ultracentrifugation and chromatography. Blue dextrane-Sepharose, folate-Sepharose and phenyl-Sepharose were used as affinity adsorbents. The optimal conditions for the adsorption and elution of the endonucleases excluding intermediate steps of dialysis and concentration were selected. A high degree of purification was achieved by a consecutive use of adsorbents with different ligands. The purified enzyme does not contain non-specific nucleases or phosphatases, is sufficiently concentrated and can be used for specific hydrolysis of DNA.

Direct and competitive radioimmunoassay (RIA) identified several antigenic determinants in hexone of adenovirus (Ad) of lower primates SA7: a species-specific, one common for Ad SA7 and SV38, as well as 2 genus-specific determinants: one common for the studied human Ad types 1 and 6, simian Ad SA7 and SV38, cattle AD of type 3, and a new determinant common for human Ad type 6 and simian Ad SA7 and SV38. It is proposed that the above genus specific determinants be designated alpha 1 and alpha 2, respectively. Indirect evidence of the occurrence in nature of rabbit Ad was obtained as sera from some nonimmunized animals precipitate purified labeled SA7 hexone, i.e. contain antibodies to the genus-specific determinant of the hexone.

Benz(a)pyrene in a concentration of 2.5 micrograms/ml produced a 3.3-fold increase in the transforming activity of simian adenovirus S5 in primary cultures of rat kidney cells. Under analogous conditions TPA increased (2.1 times) the transforming activity of DNA of human adenovirus of type I (AdI). PX5 cells (cotransformed by S5 and benz(a)pyrene) induced tumours in 100% of syngeneic and 81% xenogeneic animals. PX4 cells (transformed by S5 only) induced tumours in 60% of syngeneic animals. Cells transformed by DNA AdI and DNA AdI + TPA did not induce tumours in animals.

The buoyant density values in cesium chloride of DNA fragments of simian adenovirus SA7 obtained with restricting endonucleases of R. EcoRI, R. BamHI, R. SalI and human adenovirus type 6 DNA fragments obtained with restricting endonucleases of R. EcoRI and R. BamHI were determined. On the basis of the buoyant density values for these fragments the content of GC pairs in them was calculated. Using the known position of the fragments in the physical map of these DNAs, the distribution of GC pairs along the examined DNA molecules was constructed.

Homology of the genomes of large-plaque (lp) and small-plaque (sp) clones of simian adenovirus type 7 (SV7) was studied experimentally. Guanidine chloride helped to isolate circular DNA molecules of identical length for both clones within the measurement error (1 = 11 +/- 0.2 micrometer). A heteroduplex SV7lp--SV7sp molecule was found to have two nonhomology sites 0.5 +/- 0.3 mu and 1.0 +/- 0.5 micrometer long located at a distance of 2 and 4 micrometer from one of the ends of the molecules, respectively.