Characterization of growth and radiation response of KHT tumor cells metastatic from lung to ovary and kidney.

Female C3H/HeJ mice were inoculated intravenously with KHT sarcoma cells. Once macroscopic colonies were established in the lungs, the thoraces of the animals were locally irradiated. Despite significant lung nodule regression following treatment, animals were observed to die with ovarian and renal metastases. By irradiating the lungs at various times after intravenous tumor cell injection, it was demonstrated that ovarian and renal metastases arose only from established lung colonies and were not a consequence of the initial cell inoculum. Incidence of metastases increased from 0 to 100 per cent when the time between cell inoculation and thoracic irradiation was increased from 4 to 16 days. Once established, ovarian and renal metastases grew with a doubling time of approximately 1-2 days. Metastatic tumors in the ovaries were found to be refractory to radiation therapy because of a large component of radiation-resistant hypoxic cells. Parallel experiments utilizing male C3H/HeJ mice demonstrated metastases only in the kidneys and these grew at a growth rate similar to that seen for renal metastases in female mice. This system may serve as a model for the study of factors influencing the dissemination of tumor cells to these anatomical sites and their response to treatment.