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During 42 years several hundred nuclear tests were performed by the former USSR at the Semipalatinsk Test Site (STS, Kazakhstan), of which more than 100 were done in the atmosphere. We report here the late genetic damage of external exposure to radiation and environmental radioactive contamination in people living in Dolon, a small settlement situated in the vicinity of the STS. The comet assay was applied on DNA lymphocytes of 20 exposed women and 32 non-exposed women living at 500 km from the STS. We observed a statistically significant difference between the exposed and control groups for mean tail moment (MTM) and DNA% in the tail. The mean values of all comet assay parameters (MTM, DNA% in the tail and score) were higher in the group of women born before 1949 as compared to those born after 1950, which could reflect an effect of external irradiation in 1949 due to the most contaminating explosion. These results suggest that people exposed 50 years ago to relatively small doses of external irradiation and/or still living in an environment contaminated by small amounts of long life radionuclides, still present DNA damage which is in agreement with other cytogenetical studies performed at the same site, on the same population.

The effects of short-term gamma radiation on pea plants were investigated by exposing 5-day-old seedlings with doses ranging from 0 to 60 Gy, and studying plant growth and development over two generations after irradiation. Doses higher than 6 Gy significantly inhibited the G1 plant growth and productivity, and no seedling survived irradiation with 40 Gy and above. These effects were transmitted and were even more severe in the next generation, G2. Irradiated G1 (> or =10 Gy) and G2 (> or = 0.4 Gy) plants were significantly smaller than controls. The mean number of pods produced per plant was reduced by at least 20% at all doses in both G1 and G2. In parallel, the mean numbers of ovules and normally developed seeds per pod were significantly reduced after 10 Gy in G1 and after 0.4 Gy in G2, leading to a significant drop in seed production. This effect was correlated with a linear decrease in male fertility linked to abnormal meiosis (tetrads with micronuclei) as a function of doses from 0 to 10 Gy, in G1 and G2 plants. These long-term changes in plant development demonstrate a genomic instability induced by irradiation. However, there were neither quantitative nor qualitative changes in storage proteins in G1 seeds at any of the irradiation doses tested from 0 to 10 Gy.

The effects of low doses of ionizing radiation have been a matter of important debate over the last few years. The point of discussion concerns the validity of the linear dose-response extrapolation for low doses, used by international organizations, to establish radio-protection norms. Here, we contributed to this discussion by investigating the induction of chromosome aberrations by low to moderate doses ranging from 0 to 10 Gy in root meristem cells of 6-day-old Pisum plantlets. After acute irradiation of plantlets by a (60)Co source, the percentage of root tip meristem cells displaying chromosome aberrations was estimated immediately after irradiation and after 20 h recovery time. The dose-effect curves show non-linear responses, especially in the low dose range (0- 1 Gy), which is of particular interest. After 20 h of recovery, a steep increase of aberrations was observed for cells exposed to 0.4 Gy, followed by a plateau for doses until 1 Gy. There was an irradiation effect on plant growth during the first and second generations, showing the persistence of cell division anomalies as a long term effect of acute irradiation. This result suggests the induction of a genomic instability. Our results, in agreement with some obtained in animals, show rather non-linear dose-effect responses, with notably higher biological effects of low doses than expected.

Purpose: Retrospective analysis of the results of radiotherapy in localized prostatic adenocarcinoma. Complications were excluded., Patients and Methods: Six-hundred-and-ten T1-T2 adenocarcinomas of the prostate were treated with continuous courses of external beam radiation therapy in 19 participating Institutes between January 1983 and January 1988. The mean follow-up was 10.4 years; the mean age of patients at the beginning of radiotherapy was 68.5 years., Results: A 10-year, local control had been achieved in 86% of T1-T2 (81.4% for T2). The 5- and 10-year metastatic relapse rates were 25.3% and 30% (29% and 38.1% for T2), respectively. At 10 years, 62.4% of T1-T2 were recurrence-free; overall survival rate was 45.8% and cause-specific survival rate was 70.5%; 29.9% of T1-T2 patients were alive and disease-free. T category (TNM), pathologic grade, pelvic lymph node status, local tumor control, and obstructive ureteral symptoms were correlated with survival. The influence of pelvic nodes radiation, dose, overall treatment time, previous endocrine treatment, and transuretral resection was not significant for disease-free survival (alive and disease-free) and other endpoints., Conclusion: There was no difference between the French series (1975-1982 and 1983-1988). The results of the literature are comparable to ours. As far as prognostic factors are concerned, this report provides evidence that the explainable variables which influence survival depend on the tumor and patient status.

From 1986 to 1992, 55 cases of PPWC were treated with a conservative intent at the Regional Cancer Center (Rennes, France) and Saint-Yves Center (Vannes, France): 16 oropharyngeal posterior wall carcinoma (OP) and 39 hypopharyngeal posterior wall (HP); the mean age of the population was 60.3 years (31-81 years). A previous and simultaneous head and neck cancer was noted in 15 and 13% of cases respectively. Half of the cases (55%) were T1 T2 tumors and 82% were N0 N1. Except for three patients treated by curietherapy (5%), all patients were treated by radiotherapy (RT) alone (75%) or associated with curietherapy (7%) or partial pharyngectomy (13%). 15% received neoadjuvant chemotherapy, mainly for T3 tumors. With a followup of 4-88 months (mean: 23 months) 38% of patients are still alive; 8% of loco-regionally controlled patients died of second cancer or intercurrent disease. The tumor control was 67%. The nodes control was 90%. During the course of the disease, 19% of patients had metastases. The complete response at the end of treatment was 78%. Among these patients, 54% remained definitively free of disease. There is no difference between OP and HP. The analysis of survival curves showed the following points: significant difference between T1 T2, and T2 T3 (P < 0.05), N0 N1 and N2 N3 (P < 0.03), well differentiated histology or not (P < 0.02), RT alone or associated with curietherapy or surgery (P < 0.03) even for limited tumors T1 T2 N0 N1 (P < 0.03). There was no significant difference between group treated or not by chemotherapy even for T3 tumors. These findings do not differ if we consider either OP or HP. We conclude that OP and HP have the same prognostic factors and must be considered as the same clinical entity. For limited tumors T1 T2 N0 N1, patients managed by radiotherapy associated with complementary local treatment (conservative surgery or curietherapy) do better than patients treated by RT alone (plateau 80% at 18 months+vs plateau 25% at 12 months +). For these limited tumors, our recommendation is to treat patients by external RT (50 Gy) and curietherapy boost (20 Gy) rather than by conservative surgery and external RT (70 Gy). These two treatments have the same efficacity but the first one is expected to diminish late complications of RT. Neo adjuvant chemotherapy does not seen to improve survival even for advanced tumors. Generally speaking these results remain poor for locally advanced desease and for undifferentiated tumors. These patients need a new therapeutic approach (concomittant radio-chemotherapy, hyper or hypofonctionnated RT).

The authors report the results of a multicentric randomised trial assessing the effects on survival of neoadjuvant chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, D2-4) delivered before regional treatment in patients with squamous cell carcinoma of hypopharynx and base of tongue. 133 patients were enrolled in the study, and 121 were included in the analysis, 64 in group A (regional treatment alone) and 27 in group B (chemotherapy followed by regional treatment). Despite a high objective response rate to chemotherapy (primary tumour: 85%, 24% complete; nodes: 63%), overall survival was not significantly higher in group B than in group A.

From 1982 to 1987, a randomized phase III trial was performed in order to determine the long-term effect of induction chemotherapy before standard pelvic irradiation in stage IIb-N1, III squamous cell carcinomas of the cervix. Patients were randomized to either chemotherapy and radiotherapy (C + R group) vs radiotherapy alone (R group). Radiotherapy for all patients consisted of 50 Gy in the pelvis with a boost by external irradiation or by brachytherapy (cumulative dose of 68 Gy). The chemotherapy regimen was an association of methotrexate (10 mg/m2, D2-4), chlorambucil (4 mg/m2, D1-5), vincristine (0,7 mg/m2, D1), cisplatin (80 mg/m2, D5), given every 3 wks; at least 2 courses were to be given before assessing efficacy and 2 more courses were given to patients who responded. One hundred and fifty-one patients were fully evaluable, after a mean follow-up of 38 mths (range 2-7 years), 76 in the R arm and 75 in the C + R arm. The response rate (greater than 50%) to chemotherapy was 42.5%. After completion of treatment, the complete response rate was 86.8% in the R arm and 86.3% in the C + R arm. The 3 year disease-free survival was 58.7% in the C + R group and 54.5% in the R group, and the median survival was 39.5% and 47 months respectively (NS). The survival of patients with a complete response at the end of radiotherapy was significantly better in the C + R group (when chemotherapy had been active) than in the R group (p = 0.04). Although radiotherapy was not modified whether patients had initial chemotherapy or not, tolerance was not significantly different between the 2 groups. The data collected in this study indicate that: 1) efficacy of induction chemotherapy is the only available predictive test for long-term results, 2) tolerance to treatment is crucial for optimal chemotherapy delivery, 3) higher dose intensity of chemotherapy in cervical carcinoma is associated with a better tumor reduction, and probably a better survival.