RADIATION-INDUCED ACUTE IMMEDIATE NUCLEAR ABNORMALITIES IN ORAL-CANCER CELLS - SERIAL CYTOLOGIC EVALUATION

OBJECTIVE: To evaluate the dose-response relationship of nuclear abnor malities in tumor cells collected by serial scrape smears from oral ca ncer patients on fractionated radiotherapy. STUDY DESIGN: The study in cluded 31 patients with squamous cell carcinoma of the oral cavity tre ated by radiotherapy (60 Gy in 25 fractions; 2.4 Gy per fraction). Ser ial scrape smears were taken from each tumor before treatment and afte r delivery of various fractions, usually 2 (4.8 Gy), 5 (12.0 Gy), 8 (1 9.2 Gy) or 12 (28.8 Gy). The smears were stained by Giemsa stain and e valuated by light microscopy, and the number of micronucleated, binucl eated, nuclear budded and multinucleated cells were scored. Their rela tion to cumulative dose teas analyzed by Kruskal-Wallis one-way analys is of variance. The results were expressed in terms of 1,000 mononucle ated cells. RESULTS: Even before treatment, most of the tumors showed various abnormally nucleated cells, and, despite the high intertumoral variation (ns indicated by the high variance), all of them showed sta tistically significant dose-related increases. The mean values before treatment and after irradiation with 28.8 Gy, respectively, were 2.8 a nd 19.5 (P<,0001) for micronucleated cells, 1.5 and 8.5 (P<.000001) fo r nuclear budded cells, 8.2 and 35.5 (P<.0001) for binucleated cells, and 3.7 and 16.8 (P<.0001) for multinucleated cells. When the differen t types of nuclear abnormalities were combined and analyzed as ''abnor mally nucleated cells,'' the mean count before treatment and after 28. 8 Gy were 7.9 and 44.9 (P<.00001), respectively. CONCLUSION: The study showed that radiation-induced micronucleation, multinucleation, binuc leation and nuclear budding in ol nl cancer cells has statistically si gnificant dose-related increases that become evident in the initial fe w days of radiotherapy and that they can be differentiated well by cyt ology. This dose-response relationship and the high intertumoral varia tions suggest that serial assay of these changes has potential use for radiosensitivity prediction.