Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

Hamm, P.C.J.; Bakker, Emily; Berg, A. P. Van Den; Aardweg, G.J.M.J. van den; Visser, A.G.; Levendag, Peter C.

doi:10.1259/bjr.73.871.11089469

Cited by 4 publications

(6 citation statements)

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“…There is also a reasonable concern for a compromised immune system, due to high skin doses from an SPE, which can lead to burns. Existing evidence suggests that the best animal model for radiation induced vomiting is the ferret (121, 122) whereas the best animal model for radiation induced skin changes is the pig (123–126). Mice, on the other hand, are the most frequently utilized mammalian species for evaluation of many radiation induced biologic effects.…”

Section: Introductionmentioning

confidence: 99%

Biological effects of space radiation and development of effective countermeasures

Kennedy

2014

Life Sciences in Space Research

156

117

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As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

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Section: Introductionmentioning

confidence: 99%

Biological effects of space radiation and development of effective countermeasures

Kennedy

2014

Life Sciences in Space Research

156

117

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“…Three different levels for the incidence of moist desquamation, the ED 20 , ED 50 and ED 80 , obtained from a separate in vivo study carried out with the same strain of pig using the same irradiation set-up with the HDR-microSelectron, the same¯exible silicon template and the same anaesthetic procedures [18], are indicated for comparison. The ED 50 value (95% con®dence interval) at the skin surface was 33.6 (32.0±35.1) Gy, which corresponded to 2.7 (4.0±1.8) colonies per cm 2 , while the ED 20 and ED 80 levels corresponded with 10.4 and 0.7 colonies per cm 2 , respectively (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Determination of colony numbers in pig epidermis as an estimate for radiosensitivity. A rapid assay based on in vitro BrdU-labelling.

Aardweg

Mooi²

1999

The British Journal of Radiology

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Abstract. A rapid assay has been developed for the quantitation of colonies arising from surviving clonogenic cells in pig epidermis after irradiation. The number of surviving clonogenic cells per unit area was related to the epidermal in vivo response of moist desquamation. After irradiation with single doses, ranging from 20 to 36 Gy, skin biopsies were taken and incubated in dispase for enzymatic separation of the epidermis and dermis. Full thickness epidermal sheets were labelled with bromodeoxyuridine (BrdU) in vitro. Proliferating cells were visualized using standard immunohistochemical procedures. Cell groups containing ¢16 cells were counted as colonies. These colonies were ®rst seen on day 14/15 after irradiation. The number of colonies per cm 2 , as a function of skin surface dose, yielded a cell survival curve with a D 0 (¡SE) of 3.87¡0.57 Gy. The ED 50 for the epidermal in vivo reaction of moist desquamation corresponded with a colony density of 2.7 colonies per cm 2 . After higher doses, abundant smaller colonies of 4±8 BrdUpositive cells were seen and these were more radioresistant, as represented by higher D 0 values.Radiation-induced epidermal injury of the skin is often assessed with the use of macroscopic endpoints such as erythema and moist desquamation. In pig skin these endpoints can be evaluated at 4±6 weeks after irradiation. However, the severity and incidence of this damage may be in¯uenced by environmental factors, such as infections, partially obscuring the dose±effect relationship. To avoid these possible confounding factors a more direct approach was used, by studying colony formation from surviving epidermal clonogenic cells. There is likely to be an inverse relationship between the incidence of moist desquamation and the survival of clonogenic cells. Colony formation can be used as an estimate of radiosensitivity [1±3]. In the past, several groups have attempted to determine radiation damage (more directly) using the number of colonies arising from surviving clonogenic cells as a parameter for epidermal radiosensitivity [4±7]. Various types of assays were used, such as (i) a macroscopic in vivo colony assay for rodent skin [5±7], (ii) autoradiographs of whole epidermal sheets for the detection of proliferating cells in mouse skin [4], (iii) crosssections of pig skin viewed by light microscopy [8], or (iv) blocking cells in mitosis followed by staining with Schiff's reagents using whole epidermal sheets from biopsies of pig skin [9]. A drawback of the macroscopic colony assay is the fact that smaller colonies are easily missed, while the use of autoradiographs and cross-sections is laborious and time consuming. The assay introduced by Chen et al [9] involved three injections of vincristine, resulting in the induction of a metaphase arrest, which allowed recognition of proliferating cells by the presence of metaphases. In this assay, separation of the epidermis from the dermis was accomplished by hydrolysis with 5 N HC1 followed by teasing apart with forceps.The objective of this pap...

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“…The dwell times for each source position were optimized using the NPS such that the dose variations over a distance of 5 mm in a plane field were minimized, with the 100% isodose at the skin surface. The 95% isodose was around the basal layer, while the 80% isodose covered the dermisfat layer (for further details see Hamm et al [11]). The skin fields were irradiated with single doses of 20 Gy, 24 Gy, 27 Gy, 30 Gy, 32 Gy, 36 Gy and 40 Gy at the skin surface, with dose rates ranging from 0.9-1.7 Gy min 21 .…”

Section: Irradiationmentioning

confidence: 99%

“…Three different levels for the incidence of moist desquamation, ED 20 , ED 50 and ED 80 , as obtained from the in vivo study carried out with the same strain of pig and the same irradiation and anaesthetic procedures [11], are included for comparison. The ED 50 value (95% confidence interval) for moist desquamation at the skin surface of 33.6 (32.0-35.1) Gy corresponded with 2.7 (4.0-1.8) colonies cm 22 (Table 2).…”

Section: Irradiated Epidermismentioning

confidence: 99%

“…Data on colony formation over a period of 10-26 days after irradiation are presented. For this study, skin fields were irradiated with an iridium-192 source, since in vivo data for this type of source were already available in our laboratory [11]. Factors that could possibly influence the number of proliferating cells, such as basal cell density and epidermal thickness, were investigated in relation to field position on the flank.…”

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Changes in epidermal radiosensitivity with time associated with increased colony numbers

Aardweg¹,

Morris²,

Bywaters³

et al. 2001

BJR

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Epidermal clonogenic cell survival and colony formation following irradiation were investigated and related to radiosensitivity. A rapid in vivo/in vitro assay was developed for the quantification of colonies arising from surviving clonogenic cells in pig epidermis after irradiation. Bromodeoxyuridine (BrdU)-labelled cells in full thickness epidermal sheets were visualized using standard immunohistochemistry. In unirradiated skin, approximately 900 BrdU-positive cells mm(-2) were counted. In a time sequence experiment, BrdU-positive cell numbers increased from an average of 900 cells mm(-2) to approximately 1400 cells mm(-2) after BrdU-labelling for 2-24 h. In irradiated skin, colonies containing >/=16 BrdU-positive cells were seen for the first time at days 14/15 after irradiation. The number of these colonies per cm(2) as a function of skin surface dose yielded a cell survival curve with a D(0)-value (+/-SE) of 3.9+/-0.6 Gy. This relatively high D(0)-value is possibly due to a rapid fall off in depth dose distribution for the iridium-192 source and consequently a substantial contribution of hair follicular epithelium to colony formation. At 14/15 days after irradiation, the ED(50) level of 33.6 Gy for the in vivo response of moist desquamation corresponded with 2.7 colonies cm(-2). Surprisingly, the number of colonies increased with time after irradiation with an estimated doubling time of approximately 4 days, while the D(0)-value remained virtually unchanged. This increase in colony numbers could be due to migration of clonogenic cells, to the recruitment of dormant clonogenic cell survivors by elevated levels of cytokines, or to both. Although frequent biopsying caused increased cytokine levels, which had a systemic effect on unirradiated skin, it had no influence on colony formation in irradiated skin. Smaller colonies, containing 4-8 cells or 9-15 cells, were abundant, particularly after higher doses, which resulted in higher D(0)-values. The majority of these small colonies were abortive and did not progress to larger colonies. There was no statistical evidence for significant variations in the interanimal responses.

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Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

Cited by 4 publications

References 45 publications

Biological effects of space radiation and development of effective countermeasures

Biological effects of space radiation and development of effective countermeasures

Determination of colony numbers in pig epidermis as an estimate for radiosensitivity. A rapid assay based on in vitro BrdU-labelling.

Changes in epidermal radiosensitivity with time associated with increased colony numbers

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