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

Cancer induction is generally considered to be the most important somatic effect of low doses of ionizing radiation. It is therefore of great concern to assess the quantitative cancer risk of exposure to radiations of different quality and to obtain information on the dose-response relationships for carcinogenesis. Tissues in the human with a high sensitivity for cancer induction include the bone marrow, the lung, the thyroid and the breast in women. If the revised dosimetry estimates for the Japanese survivors of the atomic bomb explosions are correct, there is no useful data base left to derive r.b.e. values for human carcinogenesis. As a consequence, it will be necessary to rely on results obtained in biological systems, including experimental animals, for these estimates. With respect to radiation protection, the following aspects of experimental studies on radiation carcinogenesis are of relevance: Assessment of the nature of dose-response relationships. Determination of the relative biological effectiveness of radiations of different quality. Effects of fractionation or protraction of the dose on tumour development. For the analysis of tumour data in animals, specific approaches have to be applied which correct for competing risks. These methods include actuarial estimates, non-parametric models and analytical models. The dose-response curves for radiation-induced cancers in different tissues vary in shape. This is exemplified by studies on myeloid leukaemia in mice and mammary neoplasms in different rat strains. The results on radiation carcinogenesis in animal models clearly indicate that the highest r.b.e. values are observed for neutrons with energies between 0.5 and 1 MeV. On the basis of such results it might be concluded that the maximum quality factor of 10 for neutrons should be increased. Based on current evidence, an increase by a factor of 2 to 3 seems more realistic than a tenfold rise. The diversity of dose-response relationships point to different mechanisms involved in the induction of different tumours in various species and even in different strains of the same species.
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PMID:Radiation carcinogenesis in experimental animals and its implications for radiation protection. 389 67

Recent research support the idea that DNA damage is the initial event in the process of carcinogenesis. Involvement of DNA repair in the fixation of DNA damage leading to cancer has been suggested by the presence of several cancer-prone hereditary diseases associated with DNA repair deficiency. Among them, xeroderma pigmentosum has been most extensively investigated and the "SOS response" hypothesis, originally implied to the mechanism of mutagenesis in bacteria, appears to be an attractive hypothesis for the understanding of the cancer-proneness in xeroderma pigmentosum. The DNA repair of ionizing radiation damage, however, has not been clearly demonstrated in association with the process of radiation carcinogenesis, and further studies will be needed to understand the mechanisms of radiation carcinogenesis and the involvement of DNA repair in it.
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PMID:[DNA repair and carcinogenesis]. 651 96

The statistical difficulties of estimating cancer risks from low doses of a carcinogen are illustrated by examples from radiation carcinogenesis. Although more is known about dose-response relationships for ionizing radiation than for any other environmental carcinogen, estimates of cancer risk from low radiation doses have been extremely controversial; disagreements by factors of 100 or more are not uncommon. Direct estimation, based on data from populations exposed to low doses, is usually impracticable because of sample size requirements. Curve-fitting analyses, by which higher dose data determine lower dose risk estimates, require simple dose-response models if the estimates are to be statistically stable. The current level of knowledge about biological mechanisms of carcinogenesis dose not usually permit the confident assumption of a simple model, however; thus frequently the choice is between unstable risk estimates obtained using general models and statistically stable estimates whose stability depends on arbitrary model assumptions.
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PMID:Statistical limitations in relation to sample size. 733 52

The model of radiation carcinogenesis, proposed earlier by Klebanov, Rachev, and Yakovlev [8] substantiates the employment of limiting forms of the latent time distribution at high dose values. Such distributions arise within the random minima framework, the two-parameter Weibull distribution being a special case. This model, in its present form, does not allow for carcinogenesis at multiple sites. As shown in the present paper, a natural two-dimensional generalization of the model appears in the form of a Weibull-Marshall-Olkin distribution. Similarly, the study of a randomized version of the model based on the negative binomial minima scheme results in a bivariate Pareto-Marshall-Olkin distribution. In the latter case, an estimate for the rate of convergence to the limiting distribution is given.
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PMID:A bivariate limiting distribution of tumor latency time. 779 15

Epidemiological studies have shown that inhalation of radon is associated with an increased risk for bronchogenic carcinoma in uranium miners. These alpha-emitting radon daughters also represent the largest component of background radiation to the general public. In the present study, the oncogenic transforming effects of single versus multiple doses of radon-simulated alpha-particles were examined using human papillomavirus-immortalized human bronchial epithelial cells. Endpoints such as growth kinetics, resistance to serum and 12-O-tetradecanoylphorbol-13-acetate-induced terminal differentiation, anchorage-independent growth and tumorigenicity in nude mice were used to assess the various stages of transformation in the bronchial epithelial cells. We show here, for the first time, that immortalized human cells in culture can be malignantly transformed by a single 30 cGy dose of alpha-particles. Transformed cells produced progressively growing subcutaneous tumors upon inoculation into athymic nude mice. Immunofluorescent staining of keratin and isozyme analysis of the cell lines subsequently generated from these tumors indicated that the cells were of human epithelial origin. Analysis of genomic DNA from the tumorigenic cell lines using PCR amplification and restriction enzyme analysis demonstrated no point mutation at either codon 12/13 or 61 in any of the ras oncogenes examined (K-, N- and H-ras). This system provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.
Carcinogenesis 1994 Mar
PMID:Malignant transformation of human bronchial epithelial cells by radon-simulated alpha-particles. 811 24

While the most important radiobiological questions at present can be stated simply, arriving at the answers requires the development of a broad base of understanding to which collaborative interdisciplinary efforts that use a variety of techniques will make important contributions. In spite of the range of questions that remain unanswered, we probably know more about the effects of radiation than any other environmental agent. A sound and well-planned research program into the mechanisms of radiation carcinogenesis can help in many predictable ways. It will provide data needed for setting protection standards, of course, but it will also play a vital role in solving some of the enigmas of the mechanisms of carcinogenesis. In addition, the information gained by the approach focused on basic science will ultimately provide much better methods for extrapolating from cellular and animal studies to health effects in humans and thus for developing sound, science-based radiation risk estimates.
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PMID:Important unanswered questions concerning radiation risk estimates. 821 Mar 31

Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism of radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33 rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. An abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern, was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation.
Carcinogenesis 1996 Apr
PMID:Infrequent alterations of the p53 gene in rat skin cancers induced by ionizing radiation. 862 3

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radioinduced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low doses. The effects of irradiation on the gonads are also described.
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PMID:[Exposure to ionizing radiation: radiobiological and pathogenic effects (2)]. 868 52

The present paper describes the radiobiological effects induced by an exposure to ionizing radiation and their pathogenesis. The different skin reactions are described in detail because of their importance and frequency. Thus the acute skin lesions after high doses and the late effects resulting, either from high doses, or from accumulation of chronic irradiation, are studied. The main early syndromes are then characterized: neurological, gastro-intestinal, bone-marrow and prodromic. As far as the complex problem of radiocarcinogenesis is concerned, the main results derived from studies by international organizations such as the ICRP and the UNSCEAR are reported: risk coefficient of 5% per gray, for lethal radio-induced cancer, after total body irradiation, at low dose of low-LET radiation. The effects of irradiation in utero are then considered: risk of malformation after irradiation during the two first months of pregnancy and risk of mental retardation after irradiation during the third and the fourth months. Finally, the genetic risk is presented as being equal to one fourth of the risk of carcinogenesis at low-doses. The effects of irradiation on the gonads are also described.
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PMID:[Exposure to ionizing radiation: radiobiological effects and pathogenesis. 1]. 872 Sep 71

Ionizing radiation is a well-known risk factor of cancer development, but the mechanism of radiation induced carcinogenesis is not clear. Chromosomal rearrangements induced by radiation most likely are one of the principal genetic alterations resulting in malignant transformation. The chimeric BCR-ABL associated with chronic myelogenous leukemia (CML) and H4-RET oncogenes associated with thyroid papillary carcinoma are the result of a translocation and inversion, respectively. In vitro studies showed these genes were induced by high-doses of X-irradiation in cell lines. Studies also show that therapeutic external X-ray doses as high as 60 Gy for treatment of various childhood cancers including Hodgkin's disease significantly increase the risk of thyroid cancer. Therefore, we examined the induction and persistence of these chimeric genes in human thyroid tissues transplanted in scid mice after 50 Gy exposure as a function of time for 2 months to elucidate the early events of thyroid carcinogenesis. The H4-RET genes were detected on day 2 and throughout the 2 month period. On the other hand, BCR-ABL genes were detected on day 2 and were undetectable subsequently. These results suggest that ionizing radiation causes various oncogene activations, but cells with only specific gene alteration uniquely associated with thyroid carcinogenesis are selectively retained demonstrating one of the early events in the beginnings of radiation carcinogenesis in human thyroid tissues.
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PMID:Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis. 933 21


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