Differential Modulation of Specific Gene Expression Following High- and Low-LET Radiations

Woloschak, Gayle E.; Chang-Liu, Chin Mei

doi:10.2307/3577864

Cited by 81 publications

(26 citation statements)

References 16 publications

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“…C-Fos mRNA was induced in Syrian hamster embryo cells within 3 h after 0.75 Gy of X-rays or 0.9 Gy of gamma-rays (Woloschak and Chang-Liu, 1990). In contrast, no detectable c-Fos mRNA induction was observed after treatment with high-LET fission-spectrum neutrons.…”

Section: Ap-1 Activation After Irmentioning

confidence: 96%

“…Soon after AP-1 was discovered, elevations in the steady-state levels of c-Jun, Jun-B, and c-Fos mRNA after IR were reported (Higo et al, 1989;Sherman et al, 1990;Woloschak and Chang-Liu, 1990). C-Fos mRNA was induced in Syrian hamster embryo cells within 3 h after 0.75 Gy of X-rays or 0.9 Gy of gamma-rays (Woloschak and Chang-Liu, 1990).…”

Section: Ap-1 Activation After Irmentioning

confidence: 99%

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Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation

et al. 2003

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Over the past 15 years, a wealth of information has been published on transcripts and proteins 'induced' (requiring new protein synthesis) in mammalian cells after ionizing radiation (IR) exposure. Many of these studies have also attempted to elucidate the transcription factors that are 'activated' (i.e., not requiring de novo synthesis) in specific cells by IR. Unfortunately, all too often this information has been obtained using supralethal doses of IR, with investigators assuming that induction of these proteins, or activation of corresponding transcription factors, can be 'extrapolated' to low-dose IR exposures. This review focuses on what is known at the molecular level about transcription factors induced at clinically relevant (p2 Gy) doses of IR. A review of the literature demonstrates that extrapolation from high doses of IR to low doses of IR is inaccurate for most transcription factors and most IR-inducible transcripts/proteins, and that induction of transactivating proteins at low doses must be empirically derived. The signal transduction pathways stimulated after high versus low doses of IR, which act to transactivate certain transcription factors in the cell, will be discussed. To date, only three transcription factors appear to be responsive (i.e. activated) after physiological doses (doses wherein cells survive or recover) of IR. These are p53, nuclear factor kappa B(NF-jB), and the SP1-related retinoblastoma control proteins (RCPs). Clearly, more information on transcription factors and proteins induced in mammalian cells at clinically or environmentally relevant doses of IR is needed to understand the role of these stress responses in cancer susceptibility/resistance and radio-sensitivity/resistance mechanisms.

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Section: Ap-1 Activation After Irmentioning

confidence: 96%

Section: Ap-1 Activation After Irmentioning

confidence: 99%

Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation

et al. 2003

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“…These early-response genes are part of a more general cascade of genes induced by exposure to toxicants. Ionizing radiation also induces the early-response genes c-fos, c-jun, c-myc, and NF-cB (4)(5)(6); the DNA damage-inducible genes p53, Gadd45, and Cipl are also expressed (7,8). This work was conducted to determine whether crocidolite, a known human carcinogen (9), could also induce these DNA damage-inducible genes.…”

Section: Introductionmentioning

confidence: 99%

p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers.

Johnson

Jaramillo²

1997

Environ Health Perspect

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DNA damage induced by chemicals and ionizing radiation is associated with the expression of negative regulators of the cell cycle. The arrest of cells in Gl and G2 phases of the cell cycle provides time for DNA repair. Asbestos fibers are carcinogenic when inhaled by both humans and animals; however, the mechanism by which the fibers exert their effect is unknown. This work was undertaken to determine whether the expression of DNA damage-inducible genes differs between crocidolite, a fiber positive for lung tumors, and JM 100 glass microfiber, which is negative for lung tumors when inhaled by rats. Temporal and dose-related expressions of p53, Cipl, and Gadd153 proteins were determined in cultured A549 cells treated with either Union Internationale Contre le Cancer crocidolite or JM 100 for 20 hr and cultured in fresh media. Immunolabeled cells were analyzed by flow cytometry, and the increased number of proteinexpressing cells was determined by subtracting the expression in unexposed cells from exposed cells. Crocidolite induced the expression of all three proteins with a maximum expression after approximately 18 hr in fresh media. At a similar time point, JM 100 did not markedly induce the three proteins. Crocidolite also induced a dose-dependent increase in the number of cells in the G2 phase of the cell cycle. These results show that asbestos behaves like ionizing radiation and genotoxic chemicals by inducing proteins associated with DNA damage and cell-cycle arrest. The clear difference in response between crocidolite and JM 100 may help elucidate the mechanism of action of toxic and nontoxic fibers.

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“…The restriction enzyme EcoRI is a prime candidate to use as a tool to model the genomic instability-inducing effects of DNA damaging agents, due to its high activity and nuclear localization (9,10). Induction of genomic instability may not always require direct damage to DNA and may also be caused by early response genes, such as c-fos, that are triggered by a variety of external stimuli including ionizing radiation (11). Overexpression of c-fos leads to chromosomal aberrations, gene mutations and recombination (12,13) and, therefore, seems to play a role in genomic instability.…”

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confidence: 99%

Genomic instability-based transgenic models of prostate cancer

Voelkel‐Johnson¹,

Voeks²,

Greenberg³

et al. 2000

Carcinogenesis

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To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes (EcoRI and c-fos) implicated in the induction of genomic instability. Expression of the transgenes was restricted to prostate epithelial cells by coupling them to the tissuespecific, hormonally regulated probasin promoter (PB). The effects of transgene expression were examined histologically in prostate sections at time points taken from 4 to 24 months of age. The progressive presence of regions of mild-to-severe hyperplasia, low-and high-grade prostatic intra-epithelial neoplasia, and well-differentiated adenocarcinoma was observed in both PBEcoRI lines but no significant pathology was detected in the PBfos line. Prostate tissue of PBEcoRI mice was examined for expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67 are elevated and correlate with the severity of the prostatic lesions. Overall, pre-neoplastic and neoplastic stages represented in the PBEcoRI model showed similarity to corresponding early stages of the human disease. This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease.Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death in American men but its etiology is poorly understood. One in five American males will eventually develop the disease but the high rate of clinical incidence is exceeded by the prevalence of prostate carcinomas undetected until autopsy (1,2). Although several Abbreviations: PB, probasin promoter; PCNA, proliferating cell nuclear antigen; PIN, prostatic intra-epithelial neoplasia; TRAMP, transgenic adenocarcinoma mouse prostate.© Oxford University Press 1623 genetic alterations have been documented (3), critical early molecular events involved in neoplastic initiation and progression from latent prostate cancer to the aggressive form of clinical disease remain poorly understood. Therefore, animal models that faithfully represent the broad spectrum of the human disease are required. A number of animal models for prostate cancer have been developed (4) but many lack a natural environment and characterization of early and late stages is not possible. The most successful mouse models to date utilize targeted expression of the SV40 early genes (T/t antigens) that function as oncoproteins, in part, by binding to and interfering with the p53 and/or Rb tumor suppressor proteins or by interfering with protein phosphatase 2A activity (5).In an attempt to create a model for early prostate cancer, we generated transgenic mice in which the restriction enzyme EcoRI or the proto-oncogene c-fos were expressed from a truncated rat probasin promoter. This promoter has been shown to express the SV40 early ...

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Differential Modulation of Specific Gene Expression Following High- and Low-LET Radiations

Cited by 81 publications

References 16 publications

Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation

Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation

p53, Cip1, and Gadd153 expression following treatment of A549 cells with natural and man-made vitreous fibers.

Genomic instability-based transgenic models of prostate cancer

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