Polymorphisms in DNA repair genes in lung cancer patients living in a coal-mining region.

Air pollutants and ionizing radiation are well-known carcinogens involved in the pathogenesis of lung cancer, and residents of coal-mining regions are exposed routinely to these agents. Polymorphisms in DNA repair genes may be associated with an increased risk of malignant transformation. We investigated associations between the risk of lung cancer in residents of the coal-mining region and polymorphisms in the genes APEX1 (rs1130409), hOGG1 (rs1052133), XRCC1 (rs25489, rs25487), XRCC2 (rs3218536), XRCC3 (rs861539), ADPRT/PARP1 (rs1136410), XPD/ERCC2 (rs13181), XPG/ERCC5 (rs17655), XPC (rs2228001), ATM (rs1801516), and NBS1 (rs1805794).

New human single chain anti-idiotypic antibody against benzo[a]pyrene.

The nal¨ve library from the lymphocytes of healthy humans was screened by murine single-stranded idiotypic antibodies against benzo[a]pyrene (pSh). The phage clone which contained of anti-idiotypic antibody against benzo[a]pyrene, designated as A4, was chosen for further work because of highly specific to pSh. The available protein databases were searched.

Polymorphisms of GSTM1, GSTT1, GSTP1 genes and chromosomal aberrations in lung cancer patients.

Purpose: To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation.

Methods: 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR.

Generation and Characterization of Human Single-Chain Antibodies Against Polycyclic Aromatic Hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed and relocated in the environment as a result of the incomplete combustion of organic matter. Many PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to microorganisms as well as to higher systems including humans. BP is one of the most toxicologically active PAHs and is often used as a prototype for this entire class of contaminants.

Immunological disbalance in carcinogenesis.

It is postulated a conception of immunological disbalance between carcinogenesis inhibiting and stimulating antibodies (Ab). Inhibiting Ab prevent the carcinogens and estradiol but increase the progesterone penetration into the target cells. And vise versa do stimulating Ab.

Purification and characterization of mouse single-chain antibody against polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyren mainly induce lung cancer in humans. We characterized the mouse single chain antibody against benzo[a]pyren (pSh). pSh was expressed and purified as cellulose binding domain fusion (pSh-CBD).

Antisera to polycyclic aromatic hydrocarbons and their application on the detection of chemical carcinogens in blood sera of oncological patients.

Aim: To investigate the cross-reactivity of the hyperimmune antisera of animals (rabbits) and the sera of oncological patients to polycyclic aromatic hydrocarbons (PAHs) of a similar chemical structure.

Methods: Reactions of antibodies with haptens have been estimated by non-competitive and competitive ELISA with synthesized protein conjugates of PAHs as a coating antigene.

Results: All the model rabbit antisera have been stated to react with anthracene, chrysene, pyrene, benzo(a)pyrene and benz(a)anthracene irrespective of the hapten used to immunize animals.

Synthesis of polycyclic aromatic hydrocarbon-protein conjugates for preparation and immunoassay of antibodies.

The method is described dealing with the synthesis of conjugates protein-polycyclic aromatic hydrocarbons (PAHs), highly soluble in water, stable without special stabilizers and containing the minimum quantity of cross-linked products. The reaction of protein with PAH containing an aldehyde group, has been carried out in an alkaline solution, and stabilization of the conjugate has been achieved by reduction with sodium borohydride in the presence of a compound blocking the formation of an insoluble polymeric fraction. The efficiency of synthesized conjugates for the induction and immunoassay of Abs to PAH for benzo[a]pyrene is shown.

Mechanisms of HLA DR Gene Selection in Early Ontogenesis.

Hypothesis explaining the cause of MHC gene frequency variation in two consecutive generations is presented. The four stages of MHC genes selection is postulated: gamete processing, reaction of fertilization, preimplatation and implatation embryos survival, postnatal selection. On the stage of gametogenesys different adaptivity of germ cells is connected with MHC alleles.

Reaction of Immune System on Chemical Carcinogens.

Metabolism of carcinogens and their influence on the function of immunocompetent cells is quite well studied. However, well known view among immunologists and oncologists concerning the unambiguously inhibiting carcinogen action on immunity and failure of immunological surveillance is not quite correct. In 1937 H.

Effect of Immune Interactions in Mother-Fetus System on Formation of Immune Response to Main Vaccinal Antigens.

Immune disturbances in the mother-fetus system are transformed to the postnatal period in the form of different kinds of immune pathology. Do these disturbances have an effect on the formation of postvaccinal immune response? A study was made in 81 children who were 14 months old. The immune response to diphtheria and measles antigen in those children was studied in the passive hemagglutination reaction.

Genetic Aspects of Immunopathology in Prenatal and Postnatal Period.

The development of immunopathology in prenatal and postnatal periods has been studied with special refer to immune interaction character in mother-fetus system and inherited HLA DR genes. The immune variant of customary recurrent abortion has been shown to be associated with the HLA DR2 and HLA DR6 genes, with poor immune recognition of fetus HLA antigens and absence of serum suppressive factors in women. The distorted immune interactions with HLA antigens in the mother-fetus system are transformed into the neonatal period as purulent-septic diseases and hemolytic disease of the newborns.

Analysis of Antibodies to Carcinogens and Oncoproteins Revealed by Onco-Immunological Screening.

The review highlights the role of environmental carcinogens (diolepoxides of benzpyrene (BP), benzanthracene (BA) and chrysene) for origin of cancer and analyses some recent data on methods to diagnose cancer diseases. To facilitate cancer diagnosing the method of specific Ab screening has been elaborated and investigated for being applied in clinical practice. It is suggested that high environmental concentrations of discussed chemicals may lead to significant accumulation of their carcinogenic metabolites in tissues, that may finally induces origin of cancer.

New approaches to immunoprevention and immunotherapy of neoplasms.

The problems in the creation of vaccines for the prevention and treatment of neoplasms and the perspectives of their application are discussed. The positive and negative properties of the conjugates of the chemical carcinogens with proteins, DNA and enterotoxins, as well as the properties of the monoclonal anti-idiotype antibodies to the carcinogens are being analyzed. We are describing here a new technology of the anti-carcinogen vaccine production that we have developed.