Radiation induced chromosome aberrations in human foetal cells grown in vitro

1962 ◽  
Vol 11 (4) ◽  
pp. 356-389 ◽  
Author(s):  
J. A. Böök ◽  
M. Fraccaro ◽  
K. Fredga ◽  
J. Lindsten

SUMMARYThe effect of ionizing radiation, from a 100 Curie Cobalt-60 source, on diploid human cells grown in vitro has been investigated.The analysed cell populations originated from foetal brain and lung tissue. Other known variations of this material were age and sex of the foetuses, primary and first transfer cultures.The effect was measured by recording post-metaphase chromosomal aberrations in cell cultures fixed and stained 24 and 48 hours after acute irradiation. “Spontaneous” aberration frequencies were determined in matched control cultures.Although conclusions must be guarded, in view of the insufficient knowledge of factors influencing human cell populations in vitro, our observations can be summarized, tentatively, in the following main points.1. The frequency of “spontaneous” aberrations appears to vary with respect to (a) differences between the individuals from whom the biopsies were taken, (b) tissue of origin whether within or between individuals and (c) the sex of the cultured cells.The qualified estimates of the overall averages of “spontaneous” aberrations were, (a) for the cell cultures derived from foetal lung 0.7 per cent (41/5,891 scored cells) and (b) for the cell cultures derived from foetal brain 2.5 per cent (21/851 scored cells).2. In the irradiated cell cultures which received doses varying from 9-136 rads of absorbed dose the number of aberrant post-metaphases per 100 cells per rad varied from 0.10-0.15 for cultures derived from lung tissue and from 0.19-0.37 for cultures derived from brain tissue, all at 24 hours after the acute dose. At 48 hours after irradiation the frequencies were somewhat lower but the same trends remained.3. The cell cultures derived from brain tissue appear to have a higher radio-sensitivity than those derived from lung tissue. Furthermore, a sexual dimorphism is suggested because, in all series of cultures, those composed of XY cells had a higher aberration frequency as compared to those with XX cells.4. The irradiation doubling dose (for definition, see p. 27) was estimated at 15-40 rads (cf. table 7).

Author(s):  
An Aerts ◽  
Uta Eberlein ◽  
Sören Holm ◽  
Roland Hustinx ◽  
Mark Konijnenberg ◽  
...  

Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.


2012 ◽  
Vol 302 (10) ◽  
pp. G1111-G1132 ◽  
Author(s):  
Laurianne Van Landeghem ◽  
M. Agostina Santoro ◽  
Adrienne E. Krebs ◽  
Amanda T. Mah ◽  
Jeffrey J. Dehmer ◽  
...  

Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and 9 postradiation. Radiation-induced changes in number, growth, and transcriptome of the different Sox9-EGFP cell populations were determined by histology, flow cytometry, in vitro culture assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs. Irradiation caused complete crypt loss, followed by expansion and hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in culture, whereas during regeneration both Sox9-EGFP Low and High cells formed organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells exhibited transcriptomic changes linked to p53-signaling and ISC-like functions including DNA repair and reduced oxidative metabolism. These findings support a model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells contain radiation-activatable cells with ISC characteristics, and both participate in crypt regeneration.


1967 ◽  
Vol 126 (3) ◽  
pp. 423-442 ◽  
Author(s):  
Robert I. Mishell ◽  
Richard W. Dutton

A culture system for cell suspensions from mouse spleens has been described. The system provides adequate conditions for in vitro immunization on initial exposure to heterologous erythrocytes. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody. The response of cultured cells differs in two respects from that seen in vivo. There is an increase in the ability to discriminate between different varieties of homologous erythrocytes and the in vitro response does not appear to be limited by whatever mechanisms regulate the in vivo response.


2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Karen Joy Shaw ◽  
Wiley A. Schell ◽  
Jonathan Covel ◽  
Gisele Duboc ◽  
C. Giamberardino ◽  
...  

ABSTRACTCryptococcal meningitis (CM), caused primarily byCryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited, especially in resource-poor geographical regions, and mortality rates remain high despite current therapies. Here we evaluated thein vitroandin vivoactivity of several compounds, including APX001A and its prodrug, APX001, currently in clinical development for the treatment of invasive fungal infections. These compounds target the conserved Gwt1 enzyme that is required for the localization of glycosylphosphatidylinositol (GPI)-anchored cell wall mannoproteins in fungi. The Gwt1 inhibitors had low MIC values, ranging from 0.004 μg/ml to 0.5 μg/ml, against bothC. neoformansandC. gattii. APX001A and APX2020 demonstratedin vitrosynergy with fluconazole (fractional inhibitory concentration index, 0.37 for both). In a CM model, APX001 and fluconazole each alone reduced the fungal burden in brain tissue (0.78 and 1.04 log10CFU/g, respectively), whereas the combination resulted in a reduction of 3.52 log10CFU/g brain tissue. Efficacy, as measured by a reduction in the brain and lung tissue fungal burden, was also observed for another Gwt1 inhibitor prodrug, APX2096, where dose-dependent reductions in the fungal burden ranged from 5.91 to 1.79 log10CFU/g lung tissue and from 7.00 and 0.92 log10CFU/g brain tissue, representing the nearly complete or complete sterilization of lung and brain tissue at the higher doses. These data support the further clinical evaluation of this new class of antifungal agents for the treatment of CM.


1984 ◽  
Vol 10 (3) ◽  
pp. 375-378 ◽  
Author(s):  
Donald L. Shapiro ◽  
Jacob N. Finkelstein ◽  
Philip Rubin ◽  
David P. Penney ◽  
Dietmar W. Siemann

1977 ◽  
Vol 74 (3) ◽  
pp. 425-429 ◽  
Author(s):  
J. S. JENKINS ◽  
C. J. HALL

SUMMARY The metabolism of [14C]testosterone in vitro by various areas of the human foetal brain has been studied and compared with that of adult brain. The predominant metabolites were 5α-dihydrotestosterone and 5α-androstane-3α,17β-diol, and also androstenedione, and all areas of the foetal brain showed similar activity. In the foetal pituitary gland, the activity of 5α-reductase was less prominent than that of 17β-hydroxysteroid-dehydrogenase. Small quantities of oestradiol-17β were produced from testosterone by the hypothalamus, temporal lobe and amygdala only, and no aromatization could be detected in the pituitary gland. 5α-Reductase activity was much lower in adult brain tissues and no oestradiol was identified in adult temporal lobe tissue.


2013 ◽  
Vol 22 (17) ◽  
pp. 3534-3546 ◽  
Author(s):  
Brooke E. Hjelm ◽  
Bodour Salhia ◽  
Ahmet Kurdoglu ◽  
Szabolcs Szelinger ◽  
Rebecca A. Reiman ◽  
...  

1986 ◽  
Vol 64 (7) ◽  
pp. 659-666 ◽  
Author(s):  
Peter W. Gout ◽  
Robert L. Noble ◽  
Charles T. Beer

This review outlines the establishment, properties, and use of two lines of cultured Nb rat lymphoma cells. The cultured cells have retained important properties of the cancers of origin, such as dependency on prolactin for growth and a high sensitivity to antineoplastic Vinca alkaloids. The cultures have been useful for defining the hormonal dependency of the lymphomas in the animal and for studying the progression of the lymphomas from hormonal dependency to autonomy. A new, specific and highly sensitive in vitro bioassay for lactogenic hormones has been developed from one of the cultures. The use of the lymphoma cell cultures has revealed unsuspected pharmacological differences between the closely related, clinically useful antineoplastic Vinca alkaloids, vinblastine and vincristine. The lymphoma cell cultures are also useful tools for studying biochemical, cell cycle related events which follow the mitogenic stimulation of cells by a polypeptide growth factor.


1985 ◽  
Vol 6 (4) ◽  
pp. 327-337 ◽  
Author(s):  
C. F. Blackman ◽  
S. G. Benane ◽  
J. R. Rabinowitz ◽  
D. E. House ◽  
W. T. Joines

2020 ◽  
Vol 189 (2) ◽  
pp. 198-204
Author(s):  
Ehsan Mirrezaei ◽  
Saeed Setayeshi ◽  
Farideh Zakeri ◽  
Samaneh Baradaran

Abstract Cytogenetic biodosimetry is a well-known method for quantifying the absorbed dose based on measuring biological radiation effects. To correlate the induced chromosomal abberrations with the absorbed dose of the individuals, a reliable dose–response calibration curve should be established. This study aimed to use frequencies and distributions of radiation-induced dicentric chromosome aberrations to develop a standard dose–response calibration curve. Peripheral blood samples taken from six male donors irradiated by an X-ray generator up to 4 Gy were studied. Three different blood samples were irradiated by known doses, then scored blindly for verification of the proposed calibration curve. Dose estimation was also carried out for three real overexposed cases. The results showed good accordance with the other published curves. The constructed dose–response curve provides a reliable tool for biological dosimetry in accidental or occupational radiation exposures.


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