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

It is important to determine the relative contributions of genetic and environmental factors to the etiology of childhood cancer in order to elucidate the pathogenic mechanisms involved and to develop effective means of primary prevention. Geographic differences in cancer incidence as well as changes in incidence over calendar time have long been used to generate clues to possible etiologic agents. The important role of genetic factors in childhood cancer is clear, and is exemplified by the observations in retinoblastoma. The importance of the contributions of environmental factors in general and of specific factors in particular, to the etiology of cancers in children, has proven more difficult to determine. A variety of environmental factors have been implicated to varying degrees in the etiology of different childhood cancers. These factors include physical agents such as radiation, chemical agents such as nitrosamines, and organic solvents, and infectious agents such as the Epstein-Barr virus. The observations that certain compounds may act as teratogens when a prenatal exposure occurs early in pregnancy and as carcinogens when the exposure occurs late in pregnancy, suggests that there may be a continuum of teratogenesis and carcinogenesis. This finding has major implications for the possible biologic mechanisms that could be involved in childhood cancers and for the design of future research of their etiology and prevention. The etiology of childhood cancer should be viewed as an interaction of environmental factors to which the child or his parent were exposed together with varying degrees of genetically determined susceptibility of the child to the carcinogenic effects of these factors.
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PMID:Geographic and environmental factors in pediatric cancer. 371 49

Retinoblastoma (RB), cancer of the retina, occurs in an inherited form which not only predisposes the patient to bilateral RB, but also to the risk of developing secondary tumors of mesenchymal origin (osteosarcomas and fibrosarcomas). These tumors often arise in areas that were exposed to ionizing radiation during therapy and fibroblasts derived from patients with hereditary RB have been reported to be more sensitive than normal to the killing effects of ionizing radiation. Therefore, we compared diploid fibroblast cell lines derived from two hereditary RB patients (aged 1 and 3 years) with those of three normal persons (two newborns and a 2 year old) for their sensitivity to ionizing radiation-induced transformation to anchorage independence. The target cells were exposed to 60Co radiation (1.0-3.5 Gy), allowed to undergo an expression period (4-5 population doublings in 5 days), and assayed for ability to form colonies in 0.33% agar. There was no detectable difference between the RB cells' and the normal cells' response to the transforming action of the 60Co. Both kinds of cells showed a linear, dose-dependent increase in anchorage-independent cells from 100 to 800/10(6) cells assayed.
Carcinogenesis 1986 Nov
PMID:60Co radiation-induced transformation to anchorage independence of fibroblast from normal persons and patients with inherited predisposition to retinoblastoma. 376 41

In conclusion, the aniridia and the retinoblastoma stories tell us the importance of applying high-resolution cytogenetic techniques and of measuring catalase and esterase D activities when screening and investigating patients and their families. They also point to exceptional situations in carcinogenesis, and without doubt the newly devised genetic techniques, such as recombinant DNA, will allow, when applied to these conditions, a far better understanding of carcinogenesis at the molecular level--which is the important one.
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PMID:Toward clinical microcytogenetics: the aniridia and the retinoblastoma stories. 629 11

Carcinogenesis involves a complex interplay of both hereditary and environmental factors. With the exception of some cancers which may be inherited through an autosomal dominant gene (e.g., retinoblastoma), cancer causation is controlled by a multitude of genes. The murine Ah complex is an example of a well-characterized model system for studying genetic factors for carcinogenesis in mice. The Ah complex controls the induction of several xenobiotic-metabolizing enzyme activities by, e.g., polycyclic aromatic hydrocarbons (PAHs). Allelic differences at the Ah locus are associated with increased individual risk for cancer and mutation. The polyamines and their biosynthetic enzymes, especially ornithine decarboxylase (ODC), are useful probes in the study of carcinogenesis. The available evidence supports the theory that the induction of ODC activity is an essential factor in mouse skin tumorigenesis. In contrast, ODC induction is not an essential prerequisite in the induction of enzymes involved in converting carcinogens of the PAH-type to reactive intermediates capable of binding to DNA. The possible involvement of the polyamines and ODC in cancer initiation and promotion, in DNA repair processes and in genetic factors that might influence them are discussed in this review.
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PMID:Genetically determined differences in the response to carcinogens of aryl hydrocarbon hydroxylase and ornithine decarboxylase. 636 67

Skin fibroblasts from normal children and three children with a 13q deletion retinoblastoma (Rb) were exposed to cumulative low doses of gamma rays. The typical response of normal donors was a reduction in the lifespan of irradiated fibroblasts, the precocity of the decline being inversely related to the dose received. In contrast, the lifespan of one Rb cell line (Rb1) was prolonged; irradiated cells with an increased growth potential showed a higher number of cells at confluency and more cells were entering DNA synthesis phase than in non-irradiated cells. Another Rb cell line (Rb2) demonstrated a normal lifespan following irradiation but foci were observed in irradiated cultures. Cytogenetic analysis revealed no selection of abnormal clones in these cell populations. The third Rb line examined (Rb3) responded like a normal cell line. We suggest that irradiated skin fibroblasts derived from some patients with Rb are in certain cases able to express abnormal growth capacities which may be one of the manifestations of the high susceptibility of the individual's stromal cells to carcinogenic agents.
Carcinogenesis 1984 Oct
PMID:Low dose rate ionizing radiation induces increased growth capacities of d-deletion retinoblastoma skin fibroblasts. 648 51

We have developed an alternative assay system based on DNA mediated gene transfer (DMGT) for the detection of functional transforming genes which we find more sensitive and reliable than other assay systems. This approach involves selecting in tissue culture for cells which are expressing a drug-resistance marker co-transferred with the tumour DNA thus isolating the small number of cells which have taken up and are expressing exogenously added DNA. The ability of transformed cells present in this drug-resistant cell population to form tumours in athymic (nu/nu) nude mice was then used to assay for transforming genes. Using NIH3T3 and Rat 2 cells as recipients, tumours produced after DMGT with DNA from non-tumorgenic cells were only very rarely observed. Tumour induction was observed using DNA from a biopsy of a human ovary carcinoma and a spontaneous murine lung carcinoma. Two human retinoblastoma cell lines were negative for tumour induction. The transforming gene from the ovarian carcinoma was identified as c-K-ras2.
Carcinogenesis 1984 Oct
PMID:An alternative assay system for the detection of transforming genes. 648 53

Carcinogenesis is commonly considered to be a multi-step process, comprising "initiation" and "promotion" events. Skin fibroblasts from patients with hereditary retinoblastoma (RB) and familial polyposis coli (FPC) were chosen for study since their predisposition to the tumour may be due to an inherited "initiation" event which is present in every somatic cell. Thus, one might predict that skin fibroblasts from these patients might exhibit an increased susceptibility to in vitro transformation, by either tumour promoters alone or by the complete carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In the case of skin fibroblasts from RB patients, transformation as measured by the ability of cells to grow in semi-solid medium and their migration in collagen gels, did not occur with either class of agent. However, experiments involving skin fibroblasts from FPC patients, showed these cells to grow in semi-solid medium following treatment with the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alone, although their pattern of migration in collagen gels was unchanged and they were non-tumorigenic in nude mice. The clones which grew in semi-solid medium were also unaltered in terms of their migration in collagen gels and tumorigenicity in nude mice and were considered not to be completely transformed. These results are discussed in relation to theories that tumour promoters are only involved in cell selection and clonal expansion of initiated cells a second "mutational" event being required for complete transformation.
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PMID:In vitro studies of the possible mechanisms whereby tumour promoters mediate their responses. 668 Jul 26

Structural alterations in the entire coding regions (exons 1 to 27) of the retinoblastoma (RB) gene in primary human prostate cancers were investigated, using polymerase chain reaction and single strand conformational polymorphism analysis of RNA. Of 25 samples obtained from patients, four (16.4%) were found to have RB alterations. DNA sequencing of the PCR products revealed point mutations resulting in single amino-acid substitutions of exons 6 and 19 in two cases, and base deletions of exons 8 and 17 in two cases. Two of four cases with RB mutations were moderately differentiated localized tumors and other two with RB mutations were poorly differentiated tumors with metastases. Our results suggest that RB gene mutation is involved in progression steps of prostate carcinogenesis.
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PMID:Retinoblastoma gene mutations in primary human prostate cancer. 750 43

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.
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PMID:Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p. 751 41

Dysregulation of cyclin expression has been reported for several human malignancies, including breast cancer. To further investigate the role of cyclin genes in mammary tumorigenesis we analyzed the expression of cyclins D1, E and A and other cell cycle-related proteins in a series of nine N-methyl-N-nitrosourea-induced primary rat mammary tumors. Western blot analysis revealed a 10- to 15-fold increase in the level of cyclin D1 protein in most (7/9) of the tumors, when compared with normal rat mammary gland. The two tumors that did not show this increase also displayed negligible levels of the retinoblastoma protein. A moderate increase, 1.5- to 2-fold, in the level of cyclin E was observed in four tumors and three tumors displayed abnormal low molecular weight cyclin E-related proteins. None of the tumors showed amplification of the cyclin D1 or E genes when studied by Southern blot analysis. All nine tumors showed a 2- to 6-fold increase in the level of cyclin A protein. Most of the tumors also displayed a marked increase in levels of the CDK2 and CDK4 proteins. These changes did not appear to be simply a consequence of increased cell proliferation, as assessed by proliferating cell nuclear antigen analysis. Thus, aberrant expression of cyclins and other cyclin-related genes occurs frequently in mammary tumorigenesis in both rodents and humans.
Carcinogenesis 1995 Sep
PMID:Deregulated expression of cyclin D1 and other cell cycle-related genes in carcinogen-induced rat mammary tumors. 755 74


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