Dalbøge H, Madsen B, Jørgensen K D, Carlsen S
Nordisk Gentofte A/S.
Dan Med Bull. 1988 Feb;35(1):84-91.
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)
为阐明使用重组大肠杆菌菌株生产人生长激素（hGH）可能存在的风险，进行了多项研究。研究了重组大肠杆菌在大鼠胃肠道中的存活情况。结果显示，在给予10(11)个细菌后一到两天，仅在粪便中可检测到重组菌。由于重组菌对氨苄青霉素具有抗性，在用氨苄青霉素处理的大鼠中，其在胃肠道中的存活情况有所改善。然而，在氨苄青霉素治疗停止几天后，未检测到重组菌。对重组大肠杆菌的质粒DNA向其他细菌转移的研究强烈表明，用于生产hGH的重组质粒pHD117转移至大鼠肠道菌中的可能性极小。体外实验表明，推测在不可移动质粒如pHD117与接合性质粒之间发生重组后通过接合进行的转移，经计算为4×10(-6)。仅当细菌用氯化钙处理时，才观察到细菌对游离质粒DNA的摄取。对意外摄入产生hGH的细菌相关风险的评估包括对大鼠口服给药后hGH吸收情况的研究。发现约0.005%的hGH被吸收。摄入重组菌后hGH吸收的一个前提条件是细菌裂解。（摘要截短于250字）
