Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers.
A study was made of the relationship between the intrinsic radiosensitivity of human cervical tumours and the expression of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (HAP1). The radiosensitivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression levels were determined after staining of formalin-fixed paraffin-embedded tumour sections with a rabbit antiserum raised against recombinant HAP1. Both measurements were obtained on pretreatment biopsy material. All 25 tumours examined showed positive staining for HAP1, but there was heterogeneity in the level of expression both within and between tumours. The average coefficients of variation for intra- and intertumour heterogeneity were 62% and 82% respectively. There was a moderate but significant positive correlation between the levels of HAP1 expression and SF2 (r = 0.60, P = 0.002). Hence, this study shows that there is some relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The results suggest that this type of approach may be useful in the development of rapid predictive tests of tumour radiosensitivity.
Herring
C J
CJ
Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK.
West
C M
CM
Wilks
D P
DP
Davidson
S E
SE
Hunter
R D
RD
Berry
P
P
Forster
G
G
MacKinnon
J
J
Rafferty
J A
JA
Elder
R H
RH
Hendry
J H
JH
Margison
G P
GP
D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D006224:Cricetinae; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000378:metabolism*; D011817:Rabbits; D011836:Radiation Tolerance / Q000502:physiology*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology
D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase