The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine by isolated hamster pancreas cells.

The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine [( 3H]BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro was measured as DNA alkylation. Hamster tissue was incubated with [3H]BOP (0.1 mM; 20 microCi/ml) for 2 h. Initial levels of alkylation were similar, 41.7 +/- 3.7 (acinar) and 51.5 +/- 7.8 (duct) dpm/micrograms DNA. Alkylation persisted for longer in duct (t/2 greater than 46 h) than in acinar tissue (t/2 = 6 h). The faster repair of alkylation in acinar tissue was not due to acinar cell death. In rat duct tissue the level of alkylation 2 h after incubation (38.9 +/- 4.5 dpm/micrograms DNA) was similar to that in hamster ducts but declined more rapidly (t/2 = 27 h). Hamster and rat acinar and duct tissue was incubated with BOP followed by [3H]thymidine to measure DNA synthesis. BOP stimulated DNA synthesis in hamster but not in rat duct tissue or hamster acinar tissue. These data support the hypothesis that the duct tissue is the target tissue for BOP in Syrian hamsters.

Definitive external irradiation in stages A (T1) and B (T2) carcinoma of the prostate.

This is a retrospective review of records of 38 patients with clinical stage A (T1a,b), 131 with stage B1 (T2a), and 113 with B2 (T2b) histologically proven adenocarcinoma of the prostate treated with definitive irradiation. All patients have been followed for a minimum of 3 years (median follow-up: 6.5 years; maximum: 23 years). Patients were treated with high-energy photons (18-22 MV) with either 4,500 cGy to pelvic fields and a boost of about 2,000 cGy to the prostate or 6,600 cGy to the prostate and periprostatic tissues. Five patients with stage A1 (T1a) tumors had no failures. The local recurrence rate was 11% in stage T1b, 14% in T2a, and 17% in T2b tumors. Distant metastasis rates were 16% in patients with stage T1b, 20% in T2a, and 21% in T2b. The disease-free survival rate was approximately 70% at 5 years and 55% at 10 years in patients with stages T1b or T2, without significant differences among the various groups. The cause-specific survival was 90% at 5 years and 70% at 10 years in the various groups. The results are comparable to those reported in several surgical or radiation therapy series at various institutions. A significantly lower disease-free survival was observed in patients with poorly differentiated tumors (40% at 5 years) in comparison with those with well- and moderately differentiated tumors (80% DFS at 5 years) (p < .001). Likewise, the cause-specific survival was lower in patients with poorly differentiated tumors (75% at 5 years) than in the other patients (91%) (p = .0003). No difference in the local recurrence rates with various degrees of differentiation was noted. However, patients with poorly differentiated tumors had a greater incidence of distant metastasis (30%-40%) than patients with well or moderately differentiated lesions (10%-20%). Performance of transurethral resection also was associated with a higher incidence of distant metastasis (40%) in patients with stage B2 (T2b) tumors than in those diagnosed by needle biopsy (20%) (p = .12) but not in the other groups. Age, race, volume irradiated, or doses of irradiation lower or higher than 6500 cGy did not significantly affect outcome. Radiation therapy is an effective treatment for patients with stage A (T1) or B (T2) carcinoma of the prostate. Careful selection and refinement of treatment techniques, including three-dimensional treatment planning and conformal delivery irradiation or brachytherapy, may improve the management of these patients.