PURPOSE: Several investigations have demonstrated that significant biologic effects can occur in animals, animal cells, immortalized human cell lines, and primary human cells after exposure to doses of ionizing radiation in the low-dose, < or =1-10 cGy region (LDIR). However, little information is available as to how these and other observations pertain to human responses to LDIR, though such knowledge is required for reducing the uncertainty of assessing human risks due to these exposures. We therefore undertook these translational studies to begin the development of a unique data set of human cellular responses to LDIR as measured by gene expression changes when exposure occurs to a normal tissue with its complex cellular mixture and three-dimensional architecture. METHODS AND MATERIALS: Using full-thickness human skin resected during esthetic surgery, we obtained biopsy cores and exposed the tissue to LDIR ex vivo. Gene expression changes in five core regulatory genes were assessed by real-time RT-PCR. RESULTS: Results indicate that skin is a good biologic model for assessing LDIR in humans, though meticulous attention to sample processing is necessary. LDIR does produce changes in gene expression, though time- and dose-response relationships may be complex. CONCLUSION: These proof-of-principle studies have provided a crucial initial step toward validation of LDIR risk assessment models in humans. We have demonstrated the feasibility of this approach and provide initial evidence that ionizing radiation exposures as low as 1 cGy are biologically active in human skin.
PURPOSE: Several investigations have demonstrated that significant biologic effects can occur in animals, animal cells, immortalized human cell lines, and primary human cells after exposure to doses of ionizing radiation in the low-dose, < or =1-10 cGy region (LDIR). However, little information is available as to how these and other observations pertain to human responses to LDIR, though such knowledge is required for reducing the uncertainty of assessing human risks due to these exposures. We therefore undertook these translational studies to begin the development of a unique data set of human cellular responses to LDIR as measured by gene expression changes when exposure occurs to a normal tissue with its complex cellular mixture and three-dimensional architecture. METHODS AND MATERIALS: Using full-thickness human skin resected during esthetic surgery, we obtained biopsy cores and exposed the tissue to LDIR ex vivo. Gene expression changes in five core regulatory genes were assessed by real-time RT-PCR. RESULTS: Results indicate that skin is a good biologic model for assessing LDIR in humans, though meticulous attention to sample processing is necessary. LDIR does produce changes in gene expression, though time- and dose-response relationships may be complex. CONCLUSION: These proof-of-principle studies have provided a crucial initial step toward validation of LDIR risk assessment models in humans. We have demonstrated the feasibility of this approach and provide initial evidence that ionizing radiation exposures as low as 1 cGy are biologically active in human skin.
Authors: Ifigeneia V Mavragani; Danae A Laskaratou; Benjamin Frey; Serge M Candéias; Udo S Gaipl; Katalin Lumniczky; Alexandros G Georgakilas Journal: Toxicol Res (Camb) Date: 2015-08-11 Impact factor: 3.524
Authors: Shanaz A Ghandhi; Lubomir B Smilenov; Carl D Elliston; Mashkura Chowdhury; Sally A Amundson Journal: BMC Med Genomics Date: 2015-05-12 Impact factor: 3.063
Authors: Michael Abend; Ruth M Pfeiffer; Christian Ruf; Maureen Hatch; Tetiana I Bogdanova; Mykola D Tronko; Armin Riecke; Julia Hartmann; Viktor Meineke; Houda Boukheris; Alice J Sigurdson; Kiyohiko Mabuchi; Alina V Brenner Journal: PLoS One Date: 2012-07-25 Impact factor: 3.240