Genomic Instability in Chinese Hamster Cells after Exposure to X Rays or Alpha Particles of Different Mean Linear Energy Transfer

Manti, Lorenzo; M, Jamali; Prise, Kevin M.; Michael, B.D.; Trott, Klaus-Rüdiger

doi:10.2307/3579438

Cited by 68 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether by radiation or chemical mechanism, DU-UO22+ exposure is consistent with the generally accepted features associated with neoplastic transformation of cells by radiation or metal exposure including formation of sister chromatid exchanges (31,36,37) and genomic instability manifested as gene alterations (6,36,38).…”

Section: Discussionsupporting

confidence: 81%

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

Miller¹,

Blakely²,

Livengood³

et al. 1998

Environmental Health Perspectives

View full text Add to dashboard Cite

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data enxst rding the long-term health effects of internaized DU in humans. We established an in viuro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracelular and etacelular u m levels, showed that few (0.0014%) cell nuldei were hit by alph partidles. We report the ability of DU-uranyl chloride to tansform immortalized human osteoblastic cells (HOS) to the tumoriWnic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumorsuppressor protein, and elevated levels of sister chromatid nges per cell. DU-uranyl

show abstract

Section: Discussionsupporting

confidence: 81%

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

Miller¹,

Blakely²,

Livengood³

et al. 1998

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

“…It has also been observed that genomic instability leading to genetic alteration can be produced by cytoplasm or membrane irradiation [68]. The possibility of bystander effects has also been raised [69,70].…”

Section: Cytoplasm and Bystander Effectsmentioning

confidence: 99%

General aspects of the cellular response to low- and high-LET radiation

2001

View full text Add to dashboard Cite

Radiobiological studies have shown for some time that the effects of ionising radiation on cells are mainly explained by modification of the DNA. Numerous studies over the past 50 years have accumulated clear evidence of the cause-effect relationship between damage to DNA and the cytotoxic and mutagenic effects of ionising radiation. However, the path from irradiation of the cells to the induction of biological effects comprises several complex steps. The first step involves interactions between the radiation and the cellular environment. These consist of physical and chemical reactions which produce ions, excited molecules and radical species. Excitations and ionisations are complete in about 10(-15) s, and are followed by a chemical thermal equilibrium of the species produced within 10(-12) s. These species then diffuse from their site of production and provoke alterations to a variety of cellular components. This damage is detected by cellular surveillance systems, which in turn activate signalling cascades, gene transcription and enzyme recruitment, which participate in the cellular response. In most cases, cell cycle arrest occurs, allowing, according to the biological relevance of the DNA damage, either a process of DNA repair or programmed cell death (apoptosis). The accuracy of the DNA repair which is performed depends on the complexity of the DNA lesion and on the DNA repair machinery fidelity itself. Improper DNA repair can lead to mutation, chromosome aberration, genetic instability, oncogenic transformation and, ultimately, cell death.

show abstract

“…These studies are based on the premise that the bulk of DNA strand breaks induced by moderate IR doses is repaired within a few minutes or hours after IR exposure [Rogakou et al, 1999]. However, studies performed on delayed IR effects demonstrate that irradiated cells present persistent biological alterations [Jamali and Trott, 1996;Lyng et al, 1996;Manti et al, 1997]. These findings raise questions about long-term, delayed, or late consequences due to persistent DNA lesions or mutations, and the extent to which transcriptional alterations may impose a risk to humans [Falt et al, 2003;Snyder and Morgan, 2004].…”

Section: Discussionmentioning

confidence: 88%

Delayed effects of exposure to a moderate radiation dose on transcription profiles in human primary fibroblasts

Mello

Fachin

Junta

et al. 2011

Environ and Mol Mutagen

View full text Add to dashboard Cite

Ionizing radiation (IR) is used in a wide variety of medical and nonmedical applications and poses a potential threat to human health. Knowledge of changes in gene expression in irradiated cells may be helpful for the establishment of effective paradigms for radiation protection. IR-induced DNA damage triggers a complex cascade of signal transduction. Recently, genome-wide approaches have allowed the detection of alterations in gene expression across a wide range of radiation doses. However, the delayed or long-term biological effects of mild-doses of IR remain largely unknown. The main objective of the present study was to investigate the effects of a moderate dose of gamma-rays (50 cGy) on gene expression 6 days post-irradiation. Gene expression using cDNA microarrays revealed statistically significant changes in the expression of 59 genes (FDR < 0.07), whose functions are related to cell-cycle control, protein trafficking, ubiquitin cycle, Rho-GTPAse pathway, protein phosphatase signalization, oxidoreductase control, and stress response. A set of 464 genes was also selected by a less stringent approach, and we demonstrate that this broader set of genes can efficiently distinguish the irradiated samples from the unirradiated, defining a long-term IR signature in human primary fibroblasts. Our findings support the existence of persistent responses to mild doses of IR detectable by changes in gene expression profiles. These results provide insight into delayed effects observed in human primary cells as well as the role of long-term response in neoplastic transformation. Environ.

show abstract

Genomic Instability in Chinese Hamster Cells after Exposure to X Rays or Alpha Particles of Different Mean Linear Energy Transfer

Cited by 68 publications

References 23 publications

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

Transformation of Human Osteoblast Cells to the Tumorigenic Phenotype by Depleted Uranium-Uranyl Chloride

General aspects of the cellular response to low- and high-LET radiation

Delayed effects of exposure to a moderate radiation dose on transcription profiles in human primary fibroblasts

Contact Info

Product

Resources

About