There are benefits associated with the implementation of audience-specific gatekeeper training programs. Booster training sessions to address skill degradation over time are recommended.

Summary.-Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co y-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours.THE relationship between tumour size and therapeutic sensitivity has been the subject of a number of studies. Experiments from this laboratory have indicated that cells in 0-5-mm3 pulmonarv metastases of the Lewis lung (LL) tumour are considerably more radiosensitive under normal in situ conditions than those in 500-mm3 subcutaneous tumours (Shipley, Stanley and Steel, 1975). At the level of cell survival studied, the presence of a hypoxic fraction could not be detected in 0-5-MM3 pulmonary tumours, whereas the hypoxic fraction in large s.c. tumours was estimated to be 0-36. Fu, Phillips and Wharam (1976), working with the EMT6 tumour system, have also compared the radiosensitivity of large s.c. tumours with that of pulmonary nodules, and have found the smaller tumours to be considerably more radiosensitive and their hvpoxic fraction to be correspondingly lower. DeWys (1972) and Steel and Adams (1975) have found independently, in cell-survival studies with the LL tumour, that small pulmonary nodules are more sensitive to cyclophosphamide than are large s.c. tumours. Twentyman and Bleehen (1976) saw no size-dependent effect when the EMT6 tumour was treated with cyclophosphamide, although their data for the same tumour indicated that sensitivity to BCNU decreased with increasing tumour size.Any effect of tumour size on therapeutic response has important clinical implications for the use both of prophylactic cytotoxic therapy against subclinical disease and of combined modality treatment of larger tumours. The project described in this report was designed to study in greater detail the response of the LL tumour to radiation and drug treatment over a range of sizes, and to investigate the radiosensitivity of regrowing lung nodules which had been treated initially with cyclophosphamide.

Experiments are described which demonstrate that a lung-colony assay can be used to study the viability of unknown cell populations from the B16 Melanoma or the Lewis Lung Tumour. It is shown that the number of lung colonies formed can be increased by the addition of plastic microspheres to the injected cell suspension or by pre-irradiating the lungs of the recipient mice. The colony technique has been used to isolate melanotic and amelanotic cell-lines from the B16 Melanoma which were found to have different growth-rates. In vitro radiation survival curves for B16 Melanoma cells have also been established, and these have parameters in the usual range for mammalian cells.

The effects of multiple treatments with the alkylating agent chlorambucil on testicular function in the adult Wistar rat were evaluated. Weekly treatment with doses of 2.5, 5, or 10 mg/kg produced no effect either on spermatogenesis or Leydig cell function. In contrast, doses of 8 or 10 mg/kg administered twice weekly induced damage to both spermatogenesis and probably the Leydig cells. A dose-dependent decrease in spermatogonial stem-cell survival was observed with these two regimens, as assessed by counts of repopulating tubule cross sections. Although serum testosterone remained unchanged, possible Leydig cell damage was indicated by an approximate twofold increase in serum LH following treatment with either 8 or 10 mg/kg of chlorambucil twice weekly. The present results demonstrate that multiple treatments with cytotoxic drugs can be used to model the testicular damage observed in man.