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 radiosensit ivity of human cervical tumours and the expression of the DNA repair e nzyme human apurinic/apyrimidinic endonuclease (HAP1). The radiosensit ivity of clonogenic cells in tumour biopsies was measured as surviving fraction at 2 Gy (SF2) using a soft agar assay. HAP1 expression level s were determined after staining of formalin-fixed paraffin-embedded t umour 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 tumou rs. The average coefficients of variation for intra- and intertumour h eterogeneity were 62% and 82% respectively. There was a moderate but s ignificant positive correlation between the levels of HAP1 expression and SF2 (r = 0.60, P = 0.002). Hence, this study shows that there is s ome relationship between intrinsic radiosensitivity and expression of a DNA repair enzyme in cervical carcinomas. The results suggest that t his type of approach may be useful in the development of rapid predict ive tests of tumour radiosensitivity.