Increase in immunogenicity with concomitant loss of tumorigenicity of respiratory tract carcinomas during in vitro culture.

Cell lines were established in vitro from respiratory tract carcinomas induced in rats by carcinogenic, polycyclic hydrocarbons. Propagation of the carcinoma lines in vitro lead to a progressive decrease in tumorigenicity. Tumor transplantation studies in X-irradiated, immunosuppressed recipients and in immunologically reconstituted recipients suggested that the cells are rejected because of their immunogenicity, since a high incidence of tumors was observed in X-irradiated recipients but not in normal or X-irradiated, reconstituted recipients. When immunologically competent rats were immunized with cells from an in vitro tumor line, strong tumor transplantation resistance resulted. Similar immunization with the corresponding in vivo tumor line caused very little if any protection, and immunization with a non-cross-reacting sarcoma line grown in vitro did not produce immunological protection against carcinoma cell lines. A single in vivo passage of the in vitro-adapted tumor line in immunosuppressed recipients fully restored tumorigenicity. The increase in immunogenicity of carcinomas cultured in vitro appears to involve preexisting angigens indigenous to the carcinomas rather than new antigens acquired during tissue culture, such as antigens related to retroviruses, mycoplasmas, or heterologous serum.