title: The evaluation of low dose hyper-radiosensitivity in normal human skin.
abstract: OBJECTIVE
  The laboratory phenomenon of low dose hyper-radiosensitivity (LDHRS) describes an excess of cell kill at doses below 1Gy relative to that predicted by the linear quadratic model. These data have stimulated clinical investigation into LDHRS in vivo.
  
  
  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 approximately 0.5 and >1.0Gy 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 (0.5Gy TDS x 12 days) with a conventional regimen (1.5Gy OD x 12 days). Skin biopsies taken during treatment assessed BCD and proliferative index. In both studies the changes in BCD were compared using non-linear 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 approximately 0.5Gy/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 <0.5Gy or to the effects of low doses on other endpoints.
authors.affiliation: Marie Curie Research Wing, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK.
authors.forename: Jackie
authors.initials: J
authors.lastname: Harney
authors.forename: Nihal
authors.initials: N
authors.lastname: Shah
authors.forename: Susan
authors.initials: S
authors.lastname: Short
authors.forename: Francis
authors.initials: F
authors.lastname: Daley
authors.forename: Nicki
authors.initials: N
authors.lastname: Groom
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.forename: Michele I
authors.initials: MI
authors.lastname: Saunders
mesh_terms: D001707:Biopsy, Needle; D002452:Cell Count; D002455:Cell Division; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000032:analysis; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary; D014594:Uterine Neoplasms / Q000532:radiotherapy
chemical_list: D017730:Ki-1 Antigen