Antigenic Variants Isolated from a Mutagen-treated Guinea Pig Fibrosarcoma

Antigenic variants were derived from a mutagen-treated, apparently nonimmunogenic fibrosarcoma of strain 2 guinea pigs. Fibrosarcoma line 107C3, originally induced by exposure of fetal cells to a chemical mutagen, was treated in vitro with the same mutagen. Cells that survived mutagen treatment were cloned, and the clones were tested for growth in soft agar, in conventional and immunosuppressed syngeneic guinea pigs, and in nude mice. At early passages after treatment, all clones tested in conventional syngeneic guinea pigs either failed to grow intradermally or grew temporarily and then regressed. At later passages after treatment, five of eight evaluable clones grew progressively; the characteristic of intradermal tumor growth followed by tumor regression (tum^- or regressor) was a stable property of three of eight evaluable clones. The number of tumor cells required to produce progressively growing intradermal tumors in 50% of the animals (TD₅₀) of the three tum^- clones was at least 4 orders of magnitude greater than the TD₅₀ of the parent fibrosarcoma. Tum^- clones were not detected among 10 clones derived from the untreated parent tumor. Regressor clones formed colonies in soft agar and grew progressively in immuno-suppressed syngeneic guinea pigs and nude mice. Regressor clones contained tumor transplantation antigens. Guinea pigs immunized with clones that grew and regressed rejected a challenge with the parent tumor when the dose of parent tumor cells was 1 to 3 times the TD₅₀. Guinea pigs immunized by temporary growth of the parent tumor followed by excision of the local tumor and the regional lymph node did not reject a challenge with the parent tumor. These results confirm the results of experiments with murine tumors and extend the observations on tum^- clones to the guinea pig. The results indicate that in guinea pigs it is possible by immunization with tumor cell variants derived from the mutagen-treated parent tumor to produce transplantation immunity to an apparently nonimmunogenic tumor.