Safety issues related to the use of recombinant DNA-derived cell culture products. I. Cellular components

Anti-thymocyte serum (ATS) treated newborn rats were used to assess the tumorigenic potential of mammalian cell and mammalian cell culture derived substances. Injection of as much as 100 micrograms of Chinese hamster ovary (CHO) DNA, an amount in excess of 10(8) fold more than might be present in one dose of a typical final product derived from mammalian cell cultures, failed to initiate a tumor in immunosuppressed animals. In addition, injection of 10 micrograms of activated oncogene cloned from a human bladder carcinoma was also insufficient to initiate a tumor in immunosuppressed animals. Injection of some but not all CHO cell lines did result in tumor growth which upon isoenzyme analysis was verified to be of hamster origin. Of importance was the finding that recombinant tissue plasminogen activator (rt-PA) and hepatitis B surface antigen (HBsAg) vaccine failed to induce tumors in either normal or immunosuppressed rats. The results suggest that the presence of minute quantities of CHO derived nucleic acid fragments in these final products have no discernable tumorigenic potential.