Assessment of risks in connection with use of a recombinant E. coli strain for production of human growth hormone.

A number of studies were performed with the aim of elucidating possible risks in connection with the use of a recombinant E. coli strain for the production of human growth hormone (hGH). The survival of recombinant E. coli in the gastrointestinal tract in rats was studied. The results showed that the recombinants were only detectable in the faeces one to two days after the administration of 10(11) bacteria. Since the recombinants are resistant to ampicillin, survival in the gastrointestinal tract was improved in rats treated with ampicillin. However, no recombinants could be detected a few days after the discontinuation of ampicillin treatment. Studies of transfer of plasmid DNA from recombinant E. coli to other bacteria strongly indicated that the possibility of transfer of the recombinant plasmid pHD117 used in the production of hGH to enterobacteria in rats is minimal. In vitro experiments have shown that transfer by conjugation, presumably after recombination between a non mobilizable plasmid such as pHD117 and a conjugative plasmid, can be calculated to be 4 X 10(-6). An uptake of free plasmid DNA in bacteria was only observed when the bacteria were treated with CaCl2. The evaluation of risks in connection with inadvertent consumption of the hGH producing bacteria has included studies of the absorption of hGH after peroral administration to rats. Approximately 0.005% was found to be absorbed. A prerequisite for absorption of hGH after consumption of recombinants is a lysis of the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)