The tumour bed effect: a cell kinetic and histological investigation of tumours growing in irradiated mouse skin

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Abstract
Most tumours grow more slowly when implanted into pre-irradiated sites-the tumour bed effect (TBE). The TBE is usually assayed by measuring the delay for tumours growing in irradiated sites compared with that for tumours growing in mock-irradiated sites to reach a certain arbitrary, externally-measured volume. The resulting X-ray dose-response curves for the TBE are generally S-shaped, with little effect up to doses of 5 Gy, a dose-dependent effect between 5 and 20 Gy and a plateau at higher doses. In this study such a dose-dependent TBE was demonstrated for two contrasting transplantable tumours (a rapidly growing mammary adenocarcinoma and the RIF-1 fibrosarcoma) growing in the flank skin of C3H/He mice. Cell kinetic and histological methods were used to investigate the mechanism of the reduced tumour growth rate in irradiated sites. By combining information from tumour growth curves and metaphase-arrest lines, tumour cell birth and cell loss rates were estimated. In addition the necrotic and viable fractions of tissue were measured by means of Chalkley point counting. In both tumours, marked increases in cell loss rate and degree of necrosis were found to be dependent on the dose of X rays previously given to the stroma. Surprisingly, cell birth rate and mitotic index were significantly increased in mammary tumours growing in irradiated sites. The estimation of viable, as opposed to external, volume of tumours growing in sites which had received between 0 and 60 Gy X rays suggested that the conventional TBE assay method may underestimate the extent of the TBE and may distort the shape of the TBE dose response curve.