The increment of micronucleus frequency in cervical carcinoma during irradiation in vivo and its prognostic value for tumour radiocurability

A potential usefulness of micronucleus assay for prediction of tumour radio sensitivity has been tested in 64 patients with advanced stage (II B-IV B) cervical carcinoma treated by radiotherapy. The study of cellular radiosens itivity in vitro was conducted in parallel with the study of cellular damag e after tumour irradiation in vivo. Radiosensitivity of in vitro cultured p rimary cells isolated from tumour biopsies taken before radiotherapy was ev aluated using cytokinesis-block micronucleus assay. Frequency of micronucle i per binucleated cell (MN/BNC) at 2 Gy was used as a measure of radiosensi tivity. Radiation sensitivity in vivo was expressed as per cent increment o f micronucleus frequency in cells isolated from biopsy taken after 20 Gy (e xternal irradiation, 10 x 2 Gy) over the pre-treatment spontaneous micronuc leus level and was called MN20. Very low correlation (r = 0.324) was observ ed between micronucleus frequency in vitro and in vivo. Although micronucle us frequency at 2 Gy differed widely between tumours evaluated (mean MN/BNC was 0.224; range 0.08-0.416), no significant correlation was observed betw een this parameter and clinical outcome. The average increment of micronucl eus frequency after 20 Gy amounted to 193% of spontaneous level (range 60-6 10%) and was independent of spontaneous micronucleation before radiotherapy . In contrast to in vitro results, these from in vivo assay seem to have a predictive value for radiotherapy of cervix cancer. The micronucleus increm ent in vivo that reached at least 117.5% of pretreatment value (first quart ile for MN20 data set) correlated significantly with better tumour local co ntrol (P < 0.008) and overall survival (P< 0.045). Our results suggest that evaluation of increment of micronucleus frequency during radiotherapy (aft er fixed tested dose of 20 Gy) offers a potentially valuable approach to pr edicting individual radioresponsiveness and may be helpful for individualiz ation of treatment strategy in advanced stage cervical cancer.