Studies on the stimulation and suppression of deoxyribonucleic acid (DNA) synthesis in lymph node cells of mice bearing progressively growing tumours

Host responsiveness to a progressively growing methylcholanthrene (MC) induced tumour (MC6/2) was studied at varying intervals following subcutaneous (s.c.) tumour implantation by monitoring the in vitro incorporation of tritiated thymidine (3H-TdR) into lymph node cells (LNC) undergoing stimulation in vivo and concurrently determining the total numbers of the lymphoid cells present in these organs at each of the time intervals. It was found that an initial period of rapidly increasing stimulation of DNA synthesis in lymph nodes was soon followed by the onset of a stage of decrease of this activity. Within limits, the larger the tumour inoculum the stronger the initial response. The suppression of stimulation of DNA synthesis that ensued appeared to be directly related to the tumour mass and to the dose of tumour cells implanted. The total numbers of the cells accumulating in nodes also increased initially but remained elevated during the subsequent period of tumour growth. Continued presence of the tumour was essential for the increased DNA synthesis in lymph nodes since tumour removal leads to a rapid decrease to levels found in tumour-free animals. These findings demonstrate that the failure to eradicate an antigenic tumour by its host may not be solely due to "desensitizing" and "blocking" factors but that other important mechanisms are also involved. We suggest that the inability to reject the tumour in this situation is dependent in considerable measure on the development of a state of hyporeactivity in the host due to the partial inhibition of the DNA synthetic response, possibly in T cells of the tumour host, due to "suppressor factor(s)" interacting with the immunocompetent cells.