Effects of adriamycin and irradiation on beating of rat heart muscle cells in culture

Petrović, Danilo; Brown, S Susanne M.; Yatvin, Milton B.

doi:10.1016/0360-3016(77)90161-4

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…Primary fibroblasts in culture are known to go into senescence shortly after IR [8], after which terminal differentiation of these cells is induced [9]. Cultures of CM do not demonstrate cell death, nor a loss of function upon a single dose of 10,000 rad (~100 Gy) [10,11]. …”

Section: Introductionmentioning

confidence: 99%

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation

et al. 2005

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Background: During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication-and transcription-blocking lesions.

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Section: Introductionmentioning

confidence: 99%

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation

et al. 2005

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“…While the intracellular effects of HZE radiation, such as DNA damage and repair (65, 66), persistent oxidative stress (67) and cell cytotoxicity (68), have been studied, comprehensive work to elucidate how HZE particles affect heart tissue and cardiac function is still in its infancy. Previously published studies have highlighted the acute effects of high-dose radiation in cardiomyocytes (69, 70) with the primary focus on upregulation of gene transcription (71). We recently reported on the long-lasting, cyclical, time-dependent change observed in gene regulation in left ventricular cardiomyocytes up to 28 days after a single whole-body low-dose 15 cGy 56 Fe exposure (72).…”

Section: Discussionmentioning

confidence: 99%

Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart

et al. 2017

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Deep-space travel presents risks of exposure to ionizing radiation composed of a spectrum of low-fluence protons (H) and high-charge and energy (HZE) iron nuclei (e.g., Fe). When exposed to galactic cosmic rays, each cell in the body may be traversed byH every 3-4 days and HZE nuclei every 3-4 months. The effects of low-dose sequential fractionated H or HZE on the heart are unknown. In this animal model of simulated ionizing radiation, middle-aged (8-9 months old) male C57BL/6NT mice were exposed to radiation as follows: group 1, nonirradiated controls; group 2, three fractionated doses of 17 cGyH every other day (H × 3); group 3, three fractionated doses of 17 cGy H every other day followed by a single low dose of 15 cGyFe two days after the final H dose (H × 3 + Fe); and group 4, a single low dose of 15 cGyFe followed (after 2 days) by three fractionated doses of 17 cGy H every other day (Fe + H × 3). A subgroup of mice from each group underwent myocardial infarction (MI) surgery at 28 days postirradiation. Cardiac structure and function were assessed in all animals at days 7, 14 and 28 after MI surgery was performed. Compared to the control animals, the treatments that groups 2 and 3 received did not induce negative effects on cardiac function or structure. However, compared to all other groups, the animals in group 4, showed depressed left ventricular (LV) functions at 1 month with concomitant enhancement in cardiac fibrosis and induction of cardiac hypertrophy signaling at 3 months. In the irradiated and MI surgery groups compared to the control group, the treatments received by groups 2 and 4 did not induce negative effects at 1 month postirradiation and MI surgery. However, in group 3 after MI surgery, there was a 24% increase in mortality, significant decreases in LV function and a 35% increase in post-infarction size. These changes were associated with significant decreases in the angiogenic and cell survival signaling pathways. These data suggest that fractionated doses of radiation induces cellular and molecular changes that result in depressed heart functions both under basal conditions and particularly after myocardial infarction.

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“…It is well known that, at both low and high doses, the activation of multiple biological pathways by IR is dose dependent (2,76). Previous studies have characterized high-dose effects in CMs, which are functionally IR resistant to acute exposures (35,58). Gene expression in CMs at high doses of IR has shown that the primary response is to upregulate gene transcription (7).…”

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confidence: 99%

Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes

Coleman

Sasi

Onufrak

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers.

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Effects of adriamycin and irradiation on beating of rat heart muscle cells in culture

Cited by 7 publications

References 15 publications

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation

Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart

Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes

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