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OBJECTIVE: To evaluate the dose-response relationship of nuclear abnormalities in tumor cells collected by serial scrape smears from oral cancer patients on fractionated radiotherapy. STUDY DESIGN: The study included 31 patients with squamous cell carcinoma of the oral cavity treated by radiotherapy (60 Gy in 25 fractions; 2.4 Gy per fraction). Serial scrape smears were taken from each tumor before treatment and after delivery of various fractions, usually 2 (4.8 Gy), 5 (12.0 Gy), 8 (19.2 Gy) or 12 (28.8 Gy). The smears were stained by Giemsa stain and evaluated by light microscopy, and the number of micronucleated, binucleated, nuclear budded and multinucleated cells were scored. Their relation to cumulative dose was analyzed by Kruskal-Wallis one-way analysis of variance. The results were expressed in terms of 1,000 mononucleated cells. RESULTS: Even before treatment, most of the tumors showed various abnormally nucleated cells, and, despite the high intertumoral variation (as indicated by the high variance), all of them showed statistically significant dose-related increases. The mean values before treatment and after irradiation with 28.8 Gy, respectively, were 2.8 and 19.5 (P

Pedigree analysis of the oral cancer (OC) patients registered at our Centre had disclosed familial aggregation of oral cancer which hitherto has not been largely reported. There is a paucity of information on the genetic determinism for familial oral cancer predisposition. Therefore, we investigated constitutional chromosome abnormalities and bleomycin-induced chromosome sensitivity of 7 familial and 10 sporadic oral cancer patients and 14 unaffected family members (first-degree relatives) to determine whether these factors could give any clues regarding cancer-predisposing factors. Neither the oral cancer patients nor the unaffected family members showed any constitutional chromosomal abnormalities. However, with regard to bleomycin sensitivity, there was significant difference between the oral-cancer patients and unaffected relatives. The mean b/c value was 1.68 +/- 0.48 for familial OC patients, 1.12 +/- 0.36 for sporadic OC patients and 0.52 +/- 0.18 for the unaffected family members (p < 0.001). A noteworthy observation was that one unaffected family member also showed bleomycin hypersensitivity and expressed a mean b/c value of 1.32, at the initiation of the study. That patient later developed oral carcinoma. This clearly demonstrates that mutagen hypersensitivity among unaffected relatives in OC families may be related to cancer predisposition. The mutagen sensitivity study is being continued in a larger series of subjects, for the development of a cytogenetic marker for prediction of cancer susceptibility.

To identify the relationship between the radiosensitivity of oral cancers and the induction of micronucleation, nuclear budding and multinucleation (polynucleation) evaluated by serial cytology during fractionated radiotherapy.Forty-four patients with epidermoid cancer of the oral cavity receiving radiotherapy (60 Gy in 25 fractions over 5 weeks) were studied. Serial scrape smears were taken from the tumour before and during radiotherapy and stained by Giemsa and the frequency of micronucleated cells (MNC), nuclear budded cells (NBC) and multinucleated cells (PNC) was evaluated by light microscopy. After a minimum follow-up period of 30 months the patients were classified as having resistant or sensitive tumours, depending on whether the primary tumour had recurred or not within that time. Within-group and between-group analysis on the induction of the above individual parameters and two combined parameters, the micro- or multinucleated cell (MPC) count and the abnormally nucleated cell (ANC) count, was done. The counts were expressed per 1000 uni-nucleated cells.In both groups each parameter showed a statistically significant increase with dose, the increase being higher in the sensitive group. The ANC count showed the greatest increase, the mean counts before treatment and after 28.8 Gy being 24.3 and 157.8 (P0.0005), respectively, in the sensitive group and 21.0 and 65.2 (P0.0005), respectively, in the resistant group. After 28.8 Gy the sensitive tumours had significantly higher ANC (P = 0.01), MPC (P0.05) and PNC (P0.05) counts.The study shows that serial cytological assay of nuclear changes (SCANCing) during radiotherapy is a potentially useful test to predict radiosensitivity. The fact that multinucleation showed the greatest relation with radiosensitivity suggests that injury to the cytokinetic apparatus is important in determining tumour radiosensitivity.