HGM2002 Poster Abstracts: 7. Medical Genomics
POSTER NO: 385
The genetic characteristics of chromosomes of cell lines determines their tumorigenicity in nude mice
1De-Li Zhang, 2Liu-Jin LI, 2Gao-Sheng Huang, 3Shang-Gao Liu, 3Lung-Fei Yen, 4Fu-De Fang, 1Xu Shi, 1Ming-Xu Xu
The following experiments showed that the genetic characteristics of chromosomes of continuous cell lines (CCLs) determines their tumorigenicity. X strain of Hela cell line had the modal chromosomal number of 59-65 of hyper-diploid, its tumorigenicity was strong. When small amount of X strain of Hela line was inoculated into nude mice, poorly-differentiated malignant tumor from epithelium can easily developed quickly with the incidence of 100%, and can grow promptly. KB strain of Hela line had the modal chromosomal number of 57-63 of hyper-diploid, both its chromosomal genetic variation and its tumorigenicity were smaller than that of the X strain of Hela line, thus it is good to developing tumor as soon as possible when more number of this strain line was inoculated into nude mice, which has been proved by our experiment. In addition, cellular tumorigenicity can be increased if chromosome aberration is very high, because the progressively-growing malignant rhabdoid tumor (MRT) was found in all the 4 nude mice inoculated subcutaneously with 0.17ml of cell-culture of super-high concentration containing 12.75x10,000,000 Hela cells of KB strain on passages 10-11(with the rate of chromosome aberration high to 20% on passages 10-11 including 18% dicentric chromosome and 2% breakage chromosome). NM20/X strain of Hela line had the modal chromosomal number of 65-71 of hyper-diploid and hypo-tetraploid, both its chromosomal genetic variation and its tumorigenicity were greater than that of the X strain of Hela line, thus all the inoculated nude mice developed MRT (5/5). M strain of BHK-21 cell line had the definite modal chromosomal number of 42 of hypo-diploid, all the tumors inside nude mice inoculated with this strain line are morphologically similar to smooth muscle sarcomas of goodly differentiation. KA strain of BHK-21 line had the wide modal chromosomal number of 38-42 of hypo-diploid which clearly departured the normal modal chromosomal number of 44 of diploid, all the tumors inside nude mice inoculated with this strain line are malignant tumor with the incidence of MRT of 52.38%(11/21). YA strain of BHK-21 line had both modal chromosomal numbers of 38-42 of hypo-diploid and/or 70-74 of hypo-tetraploid (either had both of them or had major one of them, thus was not stable enough), all the tumors inside nude mice inoculated with this strain line are malignant tumor with the incidence of MRT of 83.33%(10/12). After being subcutaneously cultivated for 28 passages in vitro in this laboratory, BHK-21 cell line of YA strain (with the modal chromosomal number of 38-42 of hypo-diploid at the rate of 41%) was subcutaneously inoculated into nude mice and cultivated for 1 passage in vivo within 14 days, and then the developed growing malignant tumor(MT) was collected as BHK-21 cell line of NM28/YA strain on passage 0 for further continuous cultivation in vitro(with the modal chromosomal number of 70-76 of hypo-tetraploid from 2-5 passages). It is proved that hypo-diploid YA strain of BHK-21 line became hypo-tetradiploid NM28/YA strain of BHK-21 line when the former strain of in vitro cultures was inoculated into nude mice and developed tumor again. Therefore, the higher incidence of MRT (5/9) was developed following smaller number of the NM28/YA strain of BHK- 21 in vitro cultures (1.5-3.6x10,000,000/each nude mouse) was inoculated into the mice. In summary, the incidence of tumor-formation of primary feline and canine kidney cells (FKC and CKC) of diploid chromosomes in nude mice was 0% (0/32), the incidence of cancer-formation of BHK- 21 and Hela cell lines was 65/65 and 40/40, respectively. Furthermore, the greater the chromosome number variation, or the greater the modal chromosome number, or the broader the scope of modal chromosome number, or the more the chromosome number, the stronger the carcinogenicity or tumorigenicity. This study may provide potential clues for cancer gene discovery.
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