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

Beryllium is a proven bone carcinogen in rabbits, and proven pulmonary carcinogen in rats. Median effective doses or concentrations can be computed only with considerable uncertainty; they appear to be in the 10 mg area (as total dose, in divided intravenous injections, expressed as Be for zinc beryllium silicate) for rabbits, and in the 20 alpha/m3 area (as atmospheric concentration for inhalation exposures lasting for at least three months, expressed as Be for beryllium sulfate) for rats. It is also proven that, at least from inhalation, guinea pigs do not develop beryllium cancers. Epidemiologic studies in humans are thus far unconfirmed but do not show increased cancer morbidity among beryllium workers. Current research is aimed at explaining the mechanism of carcinogenic action in the susceptible species, which seems to involve nucleic acid transcriptional interference, or the species specificity, which seems to involve immune mechanisms. No experiments were reported thus far besides the carcinogenesis studies to show that beryllium is a chemical mutagen. In the species thus far tested, there appeared to be mutual exclusion of development of a delayed (cell-mediated) hypersensitivity to beryllium and development of neoplasia from beryllium. Further research on this subject might lead to new possibilities in the understanding of cancer susceptibility.
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PMID:Beryllium carcinogenesis. 41 24

The particular patterns of familial aggregations of cancer in the several families reported from our clinical resource suggest that multiple genotypes explain their diversity of cancer susceptibility. This knowledge could be of value in improving cancer control. We postulate that each particular genotype functions in concert with differential carcinogenic interactions, including a possible oncogenic virus, contributing to carcinogenesis in the susceptible patient. This reasoning is consistent with a concept of genetic heterogeneity as an explanation for familial carcinoma of the breast. This phenomenon is not unlike the current explanation for the genetics of the mucopolysaccaridoses, the lipidoses and several other major disorders of man which show genetic heterogeneity.
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PMID:Genetic heterogeneity and familial carcinoma of the breast. 126 9

A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.
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PMID:Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome. 143 48

There have been a series of reports on the association of a genetic polymorphism at the cytochrome P450 CYP2D6 gene locus with cancer susceptibility. Many of these reports have remained contradictory either because of small numbers of patients studied or because of the limitations and controversy surrounding the pharmacokinetic assay used to identify affected individuals (poor metabolizers; PMs). We have recently developed a DNA-based assay that will allow the unequivocal identification of poor metabolizers and have applied this to the study of 1635 patients with different forms of cancer. Out of 361 lung cancer patients studied no statistically significant change in the proportion of PMs relative to controls was found. However, a significant increase in the proportion of poor metabolizers or heterozygotes was seen in leukaemia, bladder cancer and melanoma patients. This could be explained by a role for CYP2D6 in carcinogen detoxification or by linkage to another cancer-causing gene.
Carcinogenesis 1992 Jun
PMID:Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility. 160 Jun 8

Examples of practical approaches to molecular epidemiology of human cancer are described. Biomarkers of carcinogen exposure or inherited host factors for cancer susceptibility are discussed. Major advances have been made in the detection of carcinogenmacromolecular adducts through the use of high performance liquid chromatography, immunoaffinity chromatography, the 32P-postlabeling assay, enzyme immunoassays, gas chromatography/mass spectroscopy and synchronous spectrophotofluorimetry. The polycyclic aromatic hydrocarbon-DNA adducts are the most extensively studied in this field and together with antibodies to these adducts found in human serum, they have become useful indicators of exposure to carcinogens. Assays for various kinds of alkyl-DNA adducts have also been developed and the presence of these adducts have been documented in human tissues. Carcinogen-protein adducts have proven to be useful molecular dosimeters of carcinogen exposure. For example, 4-aminobiphenyl hemoglobin adducts are highly correlated with exposure to tobacco smoke. The study of the molecular aspects of interindividual differences in the metabolism and activation of xenobiotics and other genetic markers [DNA-restriction fragment length polymorphisms (RFLPs), mutations, and functional loss of specific genes in carcinogenesis] is an emerging new field that is discussed in the context of genetic susceptibility to cancer. The cytochrome P450 phenotypes and acetylation phenotype are examples of genetic markers that indicate an individual's potential for metabolism of exogenous substances. Further, inherited genetic polymorphic markers, e.g., DNA-RFLPs at protooncogene loci (HRAS-1 and L-myc) have been examined in a case-control study of lung cancer. Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.
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PMID:Biochemical and molecular epidemiology of cancer. 191 Jun 3

Identification of DNA adducts in peripheral lymphocytes could serve as a means of monitoring human exposure to potential genotoxic agents. In this study, DNA from peripheral lymphocytes of smokers and nonsmokers was examined for adducts by the P1 nuclease 32P-postlabeling technique. Thin layer chromatography (TLC) maps from both groups revealed multiple DNA adducts which ranged from no adducts for one individual to six adducts for a different individual. The total DNA adduct concentrations were approximately one adduct in 10(8)-10(10) normal nucleotides. Comparison of the adduct TLC profiles revealed individual variation in both pattern and level of DNA adducts. The type and amount of adduct was not influenced by smoking history and remained unchanged in four out of six subjects who were resampled after a 1 month interval. The capacity of lymphocytes to form BaP-derived DNA adducts after a 72 h incubation with 10(-6) M [3H]BaP was measured by both high-performance liquid chromatography (HPLC) and 32P-postlabeling analysis. The in vitro adduct values detected by [3H]nucleoside concentrations on HPLC ranged from 1 to 7 fmol adduct per micrograms DNA (3.3-23.3 adducts per 10(7) nucleotides). The [3H]nucleoside values were consistent with values obtained by 32P-postlabeling of the same sample (correlation coefficient of 0.88). No relationship was apparent between the capacity of lymphocytes to form a [3H]BaP-derived adduct in vitro and the concentration of any adduct, or total adducts present in untreated lymphocytes. These results suggest that multiple DNA adducts are present in lymphocytes from nonsmokers as well as smokers, although the profile and extent of these adducts can vary among individuals. The relationship of the lymphocyte DNA adducts detected in this study to human cancer susceptibility remains to be determined.
Carcinogenesis 1990 Feb
PMID:Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by 32P-postlabeling analysis. 210 56

Interactions between molecules control intra- and intercellular physiology. Cancer is emerging as a disease in which individual molecules are either overproduced, mutated, expressed at inappropriate stages of development, or lost due to inheritance or aberrant mitotic division. The major players in this contest of cellular control are growth factors, growth factor receptors (GFRs), signal transducers, and dominant or suppressor/recessive oncogenes. The tumors most frequently removed by surgeons have been reported to have changes in one or another of these types of molecules. The concept of multistage carcinogenesis, whereby malignancy arises after a sequence of changes that are cumulative, and passed from progenitor to daughter cells, is also being defined as a sequence of molecular, genetic, and chromosomal alterations. Molecular antineoplastic therapy is in early stages of development at the laboratory bench. The future may see patients screened for cancer susceptibility, evaluated for adjuvant therapy, and chosen for particular treatment based on molecular analysis. The types of cancer operations and the scope of surgical resection may change as molecular techniques enhance oncologic treatment.
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PMID:Molecules, cancer, and the surgeon. A review of molecular biology and its implications for surgical oncology. 236 95

The development of cancer is a multistage process. The activation of proto-oncogenes and the inactivation of tumor suppressor genes play a critical role in the induction of tumors. Using human cell model systems of carcinogenesis, we have studied how oncogenes, tumor suppressor genes, and recessive cancer susceptibility genes participate in this multistep process. Normal human cells are resistant to the transforming potential of oncogenes, such as ras oncogenes, which are activated by specific point mutations. Since as many as 40% of some tumor types contain activated ras oncogenes, a preneoplastic transition in multistage carcinogenesis must involve changing from an oncogene-resistant stage to an oncogene-susceptible stage. The analysis of such critical steps in carcinogenesis using rodent systems has usually not represented the human disease with fidelity. In order to study this carcinogenic process, we have developed human cell, in vitro systems that represent some of the genetic changes that occur in cellular genes during human carcinogenesis. Using these systems, we have learned some of the functions of dominant activated-transforming oncogenes, tumor suppressor genes, and cellular immortalization genes and how they influence the carcinogenic process in human cells. Using our understanding of these processes, we are attempting to clone critical genes involved in the etiology of familial cancers. These investigations may help us to develop procedures that allow us to predict, in these cancer families, which individuals are at high risk for developing cancer.
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PMID:The current state of oncogenes and cancer: experimental approaches for analyzing oncogenetic events in human cancer. 220 69

Familial adenomatous polyposis is rare disease, but it is considered as the most important clinical model for studying cancer control and carcinogenesis in general, by its extremely high risk for colorectal cancer as well as for malignancies of diverse organs which is transmitted by autosomal dominant mode. According to Knudson, the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumor cell and same gene may be involved in both familial and non-familial cases of the tumor. The recent studies by Bodmer et al and by Solomon et al which reported on FAP locus in chromosome 5 and on loss of heterozygosity of this locus in the colorectal cancer have made an important break through in proving the Knudson's hypothesis. The epidemiological, clinical and pathological observations on FAP including our studies has been discussed in the view of these recent development of molecular biology.
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PMID:[Recent trends in studies on carcinogenesis in familial adenomatous polyposis]. 282 45

Increasing evidence suggests a role for reactive free radical oxygen species in the multi-stage events of chemical carcinogenesis. We hypothesized that variations in the level of superoxide dismutase (SOD), a major endogenous antioxidant enzyme, may account in part for variations in susceptibility to cancer induced by polycyclic aromatic hydrocarbons (PAH). The SOD activity of mammary epithelial cells from rats with varying susceptibility to dimethylbenz[a]anthracene (DMBA)-induced breast cancer was assayed. Ageing, pregnancy and previous multiple pregnancies reduce susceptibility of Sprague--Dawley female rats to DMBA. These decreases in susceptibility were correlated with increased levels of SOD activity. Only minor differences in SOD activity was observed in mammary epithelium of genetic strains of rats with differences in susceptibility to DMBA. These data suggest that, in models where physiological differences may account for variations in effectiveness of PAH to induce mammary cancer, SOD activity is inversely correlated with breast cancer susceptibility and support the hypothesis that cancer susceptibility may be partially mediated through reactive free radical oxygen intermediates.
Carcinogenesis 1986 Jul
PMID:Relationships between cellular superoxide dismutase and susceptibility to chemically induced cancer in the rat mammary gland. 308 49


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