Mass production of human × rodent cell hybrids in theinude/imouse — extent of chromosome and gene marker stability

摘要

This study shows that many somatic cell hybrids can be mass produced in the nude mouse when gram quantities are required for biochemical or other studies. Of a large series of colonies and clones isolated from diploid human × mouse (A9 or RAG) and human X Chinese hamster (CHO) hybrids, the majority could grow as tumors in the nude mouse. When the chromosomes of cells of these tumors were examined, it was found that in 10 of cases, 0 to 5 of the human chromosomes of the original hybrid were lost; in 70 , between 6 and 36 were lost; and in the remaining 20 of cases, between 36 and 82 were lost. When a human chromosome marker was detected biochemically in cells of tumors, the syntenic chromosome was always detected cytologically. The cells of daughter tumors all derived from one colony or clone generally had much greater than expected similarities in their human chromosome content, indicating that heterogeneity in the chromosome constitution of cells mass produced by this method should generally not be troublesome. Specific human chromosomes and combinations of these were lost more frequently than others, but each of the human chromosomes was retained in the cells of some of the tumors. The extent of chromosome stability appeared to be unique to each hybrid isolate. Gene products of contaminating mouse cells or fluids were sometimes detected biochemically in samples taken directly from the tumors, but not after these were maintained briefly in vitro. A few hybrids that were contaminated with mycoplasma generally failed to produce tumors in nude mice; when tumors did form, the cells had lost all or most of the human chromosomes. Thus, with noncontaminated clonal isolates the nude mouse can be used efficiently to produce large quantities of cell hybrids, which will often retain many of the human chromosomes of the original hybrid and will continue to express human gene products