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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carcinogenesis in human large intestine is a result of multiple, heterogeneous and random genetic changes. Deletion of tumor suppressor genes and activation of oncogenes appear to be important molecular events. These compromise the loss of chromosomes 5, 17, 18 or functional inactivation of FAP, p53 and DCC genes. Activation of Ki-ras and c-myc oncogenes seems to be crucial for both cell immortalization and morphology modification. Identification of genes involved in this process enables both a screening and a new classification. Also it is an important step towards a gene therapy.
Patol Pol 1992
PMID:Colorectal carcinoma as a genetic phenomenon. 129 35

310 patients were analysed with different pathological changes in the larynx, which are classified as premalignant stages and 114 cases with early cancer of the vocal cords. Out of the 310 cases, 230 cases were with chronic hypertrophic laryngitis, 44 cases with hyperkeratotic papilloma and 36 with juvenile papilloma in adults. Histologic verification of the bioptic and operative material was performed in a series of examinations. This showed that leukoplakia and one-sided pathological changes of the larynx are clinically characteristic for carcinogenesis. In chronic hypertrophy with leukoplakia, cell dysplasia occurred in 12.2% and atypia occurred in 9.8%. Hyperkeratotic papilloma underwent malignant transformation in 70.5% cases. Among the juvenile papilloma in adults with frequent recurrence of the disease, leukoplakia and dysplasia occurred periodically. Idiopathic malignant transformation of juvenile papilloma happened in only one patient. Adequate treatment of the premalignant stages effectively prevents further growth of cancer in 97% of the cases. Surgical treatment of cancer of the glottis in T1N0 and T2N0 gave a 5-year and longer survival period in 82.8%. There results were better than after radiotherapy of about 15%.
Otolaryngol Pol 1992
PMID:[Correlation of clinical and histological pictures of precancerous conditions and early-stage glottic carcinoma]. 130 35

Comparative studies of carcinogenesis were carried out in Wistar rats receiving Thyroideum Polfa and/or aflatoxin B1. Of decisive importance for the enhancement and acceleration of aflatoxin carcinogenesis, particularly in the kidneys, was the administration of Thyroideum before and during the treatment with aflatoxin B1.
Mater Med Pol
PMID:Aflatoxin carcinogenesis in Wistar rats enhanced by thyroideum POLFA. 184 13

Terminal deoxynucleotidyl transferase (TdT) was used to prepare copolymers of dA and 1,N6-ethenodeoxyadenosine (epsilon dA). When used as templates for Escherichia coli DNA polymerase I (Pol I) and compared with poly (dA), normal dTTP incorporation was not significantly affected by the presence of 7% epsilon dA. dGTP misincorporation was only slightly increased and occurred about once for every 500 epsilon dA residues. The error-prone polymerase from avian myeloblastosis virus (AMV reverse transcriptase) increased this error rate 5- to 20-fold to a maximum of 1 dG/25 epsilon dA. No dCTP misincorporation was detected with either polymerase. In transcription with E. coli DNA-dependent RNA polymerase, no errors were revealed by nearest neighbor analysis. Poly (dA) treated with chloroacetaldehyde under conditions producing the same proportion of epsilon dA (without the hydrated form) as the synthesized template behaved in the same manner with a similar low level of misincorporation of dG. Such treatment of alternating poly d(A-T) caused structural changes indicative of crosslinks but did not alter its template properties. Increasing the amount of epsilon dA in either synthesized or modified polymers greatly decreased the template activity without increasing the error rate. It is suggested that epsilon dA generally does not prevent dT incorporation but behaves as a bulky lesion which is bypassed. In contrast to the low mutagenic efficiency of epsilon dA, O4-methyldeoxythymidine (m4dT), in copolymers with dA, directed the misincorporation of 1 dG/12 m4dT with Pol I and 1 dG/3 m4dT with reverse transcriptase. Nearest neighbor analysis of transcripts showed the incorporation of 1 dG/12 m4dT. These data are in agreement with the previous reported mutagenicity of m4dT in alternating poly d(A-T, m4T).
Carcinogenesis 1984 Sep
PMID:Assessment of mutagenic efficiency of two carcinogen-modified nucleosides, 1,N6-ethenodeoxyadenosine and O4-methyldeoxythymidine, using polymerases of varying fidelity. 620 83

Chromium is an environmentally significant human carcinogen with complicated metabolism and an unknown mechanism of mutagenesis. Chromium(VI) is taken up by cells as the chromate anion and is reduced intracellularly via reactive intermediates to stable Cr(III) species. Chromium(III) forms tight complexes with biological ligands, such as DNA and proteins, which are slow to exchange. In vitro, CrCl3.6H2O primarily interacts with DNA to form outer shell charge complexes with the DNA phosphates. However, at micromolar concentrations, the Cr(III) binds to a low number of saturable tight binding sites on single-stranded M13 DNA. Additional chromium interacts in a nonspecific manner with the DNA and can form intermolecular DNA cross-links. Although high concentrations of Cr(III) inhibit DNA replication, micromolar concentrations of Cr(III) can substitute for Mg2+, weakly activate the Klenow fragment of E. coli DNA polymerase I (Pol I-KF), and act as an enhancer of nucleotide incorporation. Alterations in enzyme kinetics induced by Cr(III) increase DNA polymerase processivity and the rate of polymerase bypass of DNA lesions. This results in an increased rate of spontaneous mutagenesis during DNA replication both in vitro and in vivo. Our results indicate that chromium(III) may contribute to chromate-induced mutagenesis and may be a factor in the initiation of chromium carcinogenesis.
 ...
PMID:Effects of chromium on DNA replication in vitro. 784 35

Experimental data and clinical observations indicate that an increased expression of oncogenes or their point mutations play an essential role in the process of carcinogenesis. It was important to find out that environmental and occupational carcinogens activate cellular oncogenes and contribute to increased amounts or occurrence of mutated oncoproteins. The latter are responsible for activating mechanisms which further the neoplastic transformation of cells. The researches are mainly concerned about two oncoproteins: oncoprotein coded by the ras oncogene--called p21 protein and oncoprotein coded by the erbB-2 oncogene--called p185 protein. Investigations performed on neoplastic cells show that the neoplastic transformation process involves not only the afore-said oncogenes and their oncoproteins but also other oncogenes, and that the process itself required activating of more than one oncogene. At present, it is possible to use measurements of oncoproteins in the biological material which is easily available. Due to this fact, a number of works in which measurements of oncoproteins in blood serum were used to assess cancer risk in persons exposed to carcinogens present at the work place, have been published.
Pol J Occup Med Environ Health 1993
PMID:Oncoproteins as biomarkers of a preclinical form of cancer of the respiratory tract induced by environmental carcinogens. 801 97

Solid tumours in man are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the tumour and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. Some primary abnormalities are so characteristic as to be virtually pathognomonic for particular types of solid tumours, eg, t (11;22)(q24;q12) in Ewing's sarcoma, t (9,22)(q22;q12) in extraskeletal myxoid chondrosarcoma, t (X;18)(p11;q11) in synovial sarcoma, and t (12;16)(q13;p11) in myxoid liposarcoma. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added a growing evidence of molecular specificity emerging from recombinant DNA-studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive tumour suppressor genes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The importance of cytogenetic characterization of solid tumors is thus twofold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality identifies the presence of a neoplastic disease, and the specific type of aberration may reveal the true nature of the tumor and thus improve the diagnostic precision.
Pol J Pathol 1994
PMID:[Significance of chromosomal abnormalities in solid tumors of humans]. 817 15

Biomarkers of early health effects represent the intermediate stages of the carcinogenesis process, between the initiation and conversion stage and the clinically overt neoplastic disease. The cellular processes indicated by those markers correspond, therefore, to the promotion process. Detection of those cellular processes is extremely important, as the promotion process lasts for many years and bears some signs of being reversible. The promotion process, consisting of a range of consecutive cellular changes involves, among others, activation of proto-oncogens and their transformation into oncogens, and inactivation of the suppressor genes. Therefore, the possibility of observing the trends of those changes by monitoring protein products of the oncogens and suppressor genes in the easily available material (blood, urine) is very useful. Inhibition of intercellular communication seems to play an extremely important role in the complex mechanism of transformation of a normal cell into a neoplastic one. During the carcinogenic process promotion stage, the inhibition is associated with the proteins which form the intercellular junctions and participate in cellular adhesion. That group of proteins includes carcinoembryonal antigen (CEA) and tissue polypeptide antigen (TPA), the tumour antigens which have been known for years. The possible relationship between increased TPA and CEA concentrations is supported not only by the data from the oncology but also by the data from the studies on populations exposed to agents known to increase the risk of neoplastic disease.
Pol J Occup Med Environ Health 1993
PMID:Biological markers of early health effects in the assessment of the risk of cancer in people exposed to environmental carcinogens. 821 6

Genotoxical agents as PAH, nitrosamines, aromatic amines located in tobacco smoke are responsible for disorders of structure and function of DNA chromosomes, proteins and also initiation of carcinogenesis. DNA adducts are recognized as measure of the biological effective dose of exposure to environmental genotoxicant. So far most studies on DNA adducts after human exposure to tobacco smoke have ben carried out on white blood cells, lungs and oral cavities tissue. The aim of this work was estimation of relationship between state of neoplastic disease (TNM system) and number of aromatic DNA adducts. The subject were 37 patients with primary larynx tumor. In every case histopathological investigation revealed squamous cell carcinoma. There were 33 total and 4 partial laryngectomies performed. From tumour and nontumour larynx tissue DNA was isolated. Analysis of DNA adducts was performed by the 32P-postlabelling method. The results were characterized by individual differentiation. The highest level of DNA adducts was found in larynx tumour cells. In case of strong smokers (30-40 cigarettes per day) the level of aromatic adducts was higher then in non- or ex-smokers. In both tissues (tumour and non-tumour) the highest level of aromatic adducts was in T3 stage, the lowes in cause of T2 stage. In tissues with T4 stage the level of DNA adducts was intermediate. One has been observed decrease tendency in level of DNA adducts which is connected with increase of TNM stage.
Otolaryngol Pol 1995
PMID:[Estimation of aromatic DNA adduct levels in laryngeal tumors in relation to cancer staging]. 871 63

The importance of DNA adducts in carcinogenesis had been discussed. The 32P-postlabelling method was developed as a quantitative technique to measure the level of different DNA adducts including adducts in human DNA. The elevated level of DNA adducts was found in white blood cells in persons exposed environmentally and occupationally to high concentrations of PAHs (polycyclic aromatic hydrocarbons) in the ambient air. Tobacco also generated higher level of DNA adducts both in lymphocytes and laryngeal tissues of smokers. Exposure to styrene has been of interest world-wide because of the very high exposure and persistence of adducts in DNA of lamination workers.
Acta Biochim Pol 1996
PMID:DNA adducts in environmental, occupational and life-style studies in human biomonitoring. 886 75


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