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The evaluation of low dose hyper-radiosensitivity in normal human skin

Harney, J; Shah, N; Short, S; Daley, F; Groom, N; Wilson, GD; Joiner, MC; (2004) The evaluation of low dose hyper-radiosensitivity in normal human skin. Radiotherapy and Oncology , 70 (3) pp. 319-329. 10.1016/j.radonc.2004.01.015.

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Abstract

Background and purpose: The laboratory phenomenon of low dose hyper-radiosensitivity (LDHRS) describes an excess of cell kill at doses below 1 Gy relative to that predicted by the linear quadratic model. These data have stimulated clinical investigation into LDHRS in vivo. Patients and methods: Skin was used as a model of normal human tissue. Two studies were initiated investigating the response to low doses of radiation. Study 1 compared once daily skin doses of similar to0.5 and > 1.0 Gy in 24 patients receiving pelvic radiotherapy. Skin biopsies before and during radiotherapy were analysed histologically to assess the basal cell density (BCD). Study 2 compared two regimens of equal dose/time intensity-an ultrafractionated regimen (0.5 Gy TDS X 12 days) with a conventional regimen (1.5 Gy OD X 12 days). Skin biopsies taken during treatment assessed BCD and proliferative index. In both studies the changes in BCD were compared using nonlinear regression analysis. Results: Study 1. The results show a significantly greater reduction in BCD in the low dose group when BCD is plotted against dose. This effect is lost when BCD is plotted against time Study 2. The results demonstrate a significantly greater reduction in BCD in the higher dose/fraction arm. The proliferative response was similar in both treatment groups. Conclusions: These data suggest that LDHRS does not occur in skin following doses of similar to0.5 Gy/fraction when regimens of equal dose/time intensity are compared. As only small volumes of normal tissue were irradiated it is difficult to predict the biological relevance of this with respect to larger field low dose per fraction irradiation regimens or risk of cancer induction. Equally we cannot extrapolate to effects resulting from exposure to doses < 0.5 Gy or to the effects of low doses on other endpoints. (C) 2004 Elsevier Ireland Ltd. All fights reserved

Type: Article
Title: The evaluation of low dose hyper-radiosensitivity in normal human skin
DOI: 10.1016/j.radonc.2004.01.015
Additional information: WoS ID: 000221151200015 JournalEnglishArticle40ELSEVIER SCI IRELAND LTDARCHAMBEAU JO, 1995, INT J RADIAT ONCOL, V31, P1171; ARCHAMBEAU JO, 1988, INT J RADIAT ONCOL, V15, P1383; ARCHAMBEAU JO, 1984, RADIAT RES, V98, P254; BAUER FW, 1980, BRIT J DERMATOL, V102, P629; BOEZEMAN JBM, 1987, CELL TISSUE KINET, V20, P90; CASTELIJNS FACM, 1998, HISTOCHEM J, V30, P869; DEMARE S, 1990, ARCH DERMATOL RES, V282, P126; DESDOUETS C, 1995, PROG CELL CYC RES, V1, P115; DORNER D, 2002, RADIOTHERAPY ONCO S1, V64, PS57; FOWLER JF, 1989, BRIT J RADIOL, V62, P679; GERDES J, 1984, J IMMUNOL, V133, P1710; GLADE CP, 1996, ARCH DERMATOL RES, V288, P203; HAMILTON CS, 1996, RADIOTHER ONCOL, V40, P23; HEENEN M, 1998, DERMATOLOGY, V197, P123; HOPEWELL JW, 1990, INT J RADIAT BIOL, V57, P751; JOINER MC, 1986, INT J RADIAT BIOL, V49, P565; JOINER MC, 2001, INT J RADIAT ONCOL, V49, P379; JOINER MC, 1988, RADIAT RES, V114, P385; JOINER MC, 1993, RECENT RES CANCER, V130, P27; LANDBERG G, 1993, CELL PROLIFERAT, V26, P427; MORRIS GM, 1989, CELL TISSUE KINET, V22, P213; MORRIS GM, 1985, CELL TISSUE KINET, V18, P407; NYMAN J, 1991, ACTA ONCOL, V30, P753; NYMAN J, 1994, RADIOTHER ONCOL, V33, P117; ONUMA H, 2001, ARCH DERMATOL RES, V293, P133; PARKINS CS, 1986, BR J CANC S, V7, P320; PENNEYS NS, 1970, ARCH DERMATOL, V101, P323; PHILIPS A, 1998, CR SEANCES SOC BIOL, V192, P223; PINKUS H, 1952, J INVEST DERMATOL, V19, P431; POTTEN C, 1985, RAD SKIN, P182; SCOTT RJ, 1991, J PATHOL, V165, P173; THAMES HD, 1994, INT J RADIAT BIOL, V56, P457; TURESSON I, 2001, ACTA ONCOL, V8, P941; TZAPHLIDOU M, 1997, INT J RADIAT BIOL, V71, P109; VANDENAARDWEG GJMJ, 2001, BRIT J RADIOL, V74, P434; VANDENAARDWEG GJMJ, 1999, BRIT J RADIOL, V72, P1104; VANERP PEJ, 1989, AM J PATHOL, V135, P865; VANERP PEJ, 1987, J INVEST DERMATOL, V89, P312; WONG CS, 1992, RADIOTHER ONCOL, V23, P176; WOUTERS BG, 1997, RADIAT RES, V148, P4350MAR817AUCLAREHarney J Mt Vernon Hosp, Rickmansworth Rd,Marie Curie Res Wing, Northwood HA6 2RN, Middx, EnglandRADIOTHER ONCOLCUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND
Keywords: basal cell density, BASAL-CELL DENSITY, CANCER, COLONY NUMBERS, FRACTION, HUMAN EPIDERMIS, hyper-radiosensitivity, IN-VIVO, IRRADIATION, KI-67, LINEAR-QUADRATIC MODEL, low dose hyper- radiosensitivity, MOUSE SKIN, NUCLEAR ANTIGEN, PIG EPIDERMIS, proliferation, RADIATION, radiotherapy, response, RISK, skin, VOLUME
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/7088
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