Low-doses of ionising radiation induce melanoma metastases and trigger theimmune system-adrenal axis feedback loop

Low-doses of ionising radiation are frequently implicated in triggering and /or accelerating the growth of skin and other malignancies. It seemed proba ble that: the radiation at similar dose levels might initiate metastasis fr om already existing rumours. Highly pigmented human melanoma xenograft that had lost its ability for a spontaneous metastasising and grown subcutaneou sly in athymic mice was exposed to very low and well-defined doses of ionis ing radiation to determine whether low linear energy transfer radiation can restore metastatic potential of the tumour. To ensure that all effects der ived from radiation-activated neoplastic cells only, I-131 was delivered se lectively to the cutaneous melanoma instead of using the, external beam. Th e direct response of these tumours to radiation was monitored by determinin g the growth rare of the lesions. Histopathological methods were employed t o detect metastases, The lowest radiation dose of approximately 6 cGy depos ited in the tumours initiated metastatic spread in all animals. Gradual inc rease of the radiation doses diminished both the frequency of the appearanc e of metastases and their distance from the primary lesions. There were no metastases from non-irradiated melanomas. The highest dose used (60 cGy) di d not affect significantly the growth of cutaneous (primary) humours, but: lower doses that enhanced inflammatory infiltration of the lesions reduced tumour growth. Such radiation-stimulated immune responses were accompanied by increased pigmentation in cutaneous lesions and activation of the adrena l cortex indicating that the immune system-adrenal axis feedback loop had b een triggered. The results demonstrate that very law-doses of ionising radi ation induce melanoma metastases. The phenomenon is accompanied by the stim ulation of the immune system-adrenal axis feedback loop that regulates eico sanoid synthesis, thereby suggesting an involvement of these molecules in t he process. Radiation doses approaching the therapeutic level do not initia te melanoma dissemination. (C) 1999 Elsevier Science Ltd. All rights reserv ed.