The occurrence of apoptosis, abnormal mitoses, cells dying in mitosis and micronuclei in a human melanoma xenograft exposed to single dose irradiation.

The mechanisms of cell loss, the cell proliferation and the immediate growth response were investigated in a human melanoma xenograft given single dose irradiation with 7.5 Gy and 15.0 Gy, respectively. The frequencies of apoptotic cells, mitoses, abnormal mitoses, cells dying in mitosis and micronuclei, were scored in histological sections. In the untreated xenograft, the occurrence of micronuclei and abnormal mitoses indicated the presence of reproductively dead cells. Cell loss manifested itself through the appearance of apoptosis, cells dying in mitosis and necrosis. After irradiation, the cell proliferation was temporarily inhibited due to a radiation induced division delay. When proliferation resumed, there was a dose-dependent increase in the frequencies of abnormal mitoses and micronuclei and thus in the fraction of reproductively dead cells. The incidence of cell loss through apoptosis and cells dying in mitosis also increased. This cell loss probably reduced transiently the fraction of reproductively dead cells, and accounted for the reduced amount of tumour cells the first days after 15.0 Gy irradiation. The incidence of apoptotic cell loss and micronuclei decreased, and the incidence of normal mitoses increased when tumour growth resumed.