Abstract
BackgroundThere is a crucial shortage of methods capable of determining the extent of accidental exposures of human beings to ionizing radiation. However, knowledge of individual exposures is essential for early triage during radiological incidents to provide optimum possible life-sparing medical procedures to each person.Methods and FindingsWe evaluated immunocytofluorescence-based quantitation of γ-H2AX foci as a biodosimeter of total-body radiation exposure (60Co γ-rays) in a rhesus macaque (Macaca mulatta) model. Peripheral blood lymphocytes and plucked hairs were collected from 4 cohorts of macaques receiving total body irradiation doses ranging from 1 Gy to 8.5 Gy. Each cohort consisted of 6 experimental and 2 control animals. Numbers of residual γ-H2AX foci were proportional to initial irradiation doses and statistically significant responses were obtained until 1 day after 1 Gy, 4 days after 3.5 and 6.5 Gy, and 14 days after 8.5 Gy in lymphocytes and until 1 day after 1 Gy, at least 2 days after 3.5 and 6.5 Gy, and 9 days after 8.5 Gy in plucked hairs.ConclusionThese findings indicate that quantitation of γ-H2AX foci may make a robust biodosimeter for analyzing total-body exposure to ionizing radiation in humans. This tool would help clinicians prescribe appropriate types of medical intervention for optimal individual outcome. These results also demonstrate that the use of a high throughput γ-H2AX biodosimeter would be useful for days post-exposure in applications like large-scale radiological events or radiation therapy. In addition, this study validates a possibility to use plucked hair in future clinical trials investigating genotoxic effects of drugs and radiation treatments.
Highlights
In addition to routine therapeutic radiation exposures, substantial individual exposure to ionizing radiation may result from radiological accidents and other incidents [1,2]
These findings indicate that quantitation of c-H2AX foci may make a robust biodosimeter for analyzing totalbody exposure to ionizing radiation in humans
Lymphocytes from individuals subjected to low doses of ionizing radiation (IR) from radiological diagnostic or therapeutic treatments [6,7,8,9] and from humans traveling in space [10] were found to exhibit elevated levels of c-H2AX foci and biodosimetry applications for the immunocytofluorescence c-H2AX foci assay has been advocated ([11]; reviewed in [5] and [12])
Summary
In addition to routine therapeutic radiation exposures, substantial individual exposure to ionizing radiation may result from radiological accidents and other incidents [1,2]. One major result from radiation exposure is the formation of DNA double strand breaks (DSBs), considered one of the most dangerous lesions for the induction of genomic alterations and cancer at low levels and substantial morbidity at higher levels. Lymphocytes from individuals subjected to low doses of IR from radiological diagnostic or therapeutic treatments [6,7,8,9] and from humans traveling in space [10] were found to exhibit elevated levels of c-H2AX foci and biodosimetry applications for the immunocytofluorescence c-H2AX foci assay has been advocated ([11]; reviewed in [5] and [12]). Knowledge of individual exposures is essential for early triage during radiological incidents to provide optimum possible life-sparing medical procedures to each person
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