TY - JOUR
T1 - The presence of amplified regions affects the stability of chromosomes in drug-resistant Chinese hamster cells
AU - Miele, Mariangela
AU - Bonatti, Stefania
AU - Menichini, Paola
AU - Ottaggio, Laura
AU - Abbondandolo, Angelo
PY - 1989
Y1 - 1989
N2 - The stability of chromosomes carrying amplified CAD (carbamyl phosphate synthetase-aspartate transcarbamylase-dihydroorotase) or DHFR (dihydrofolate reductase) genes was studied in V79 Chinese hamster cell derivatives resistant to PALA (N-phosphonacetyl-l-aspartate) and MTX (methotrexate), respectively. Cells were maintained in the presence of the selective drugs during the study. In both metaphase chromosomes and interphase nuclei, amplified regions were localizaed by in situ hybridization. In MTX-resistant cells, the amplification-bearing chromosome moved sluggishly at anaphase and gave rise to bud-shaped formations in interphase nuclei. It is suggested that these buds could eventually separate as micronuclei. In both MTX- and PALA-resistant cells, amplified DNA was observed in micronuclei in interphase and in displaced chromosomes in metaphase. Finally, amplification-bearing dicentric chromosomes were found in both drug-resistant cell lines. Cumulatively, these observations indicate that the presence of the amplified region in a chromosome renders it unstable: chromosomes bearing an amplified region tended to be excluded from cells, and rearrangements were more frequent than in normal chromosomes.
AB - The stability of chromosomes carrying amplified CAD (carbamyl phosphate synthetase-aspartate transcarbamylase-dihydroorotase) or DHFR (dihydrofolate reductase) genes was studied in V79 Chinese hamster cell derivatives resistant to PALA (N-phosphonacetyl-l-aspartate) and MTX (methotrexate), respectively. Cells were maintained in the presence of the selective drugs during the study. In both metaphase chromosomes and interphase nuclei, amplified regions were localizaed by in situ hybridization. In MTX-resistant cells, the amplification-bearing chromosome moved sluggishly at anaphase and gave rise to bud-shaped formations in interphase nuclei. It is suggested that these buds could eventually separate as micronuclei. In both MTX- and PALA-resistant cells, amplified DNA was observed in micronuclei in interphase and in displaced chromosomes in metaphase. Finally, amplification-bearing dicentric chromosomes were found in both drug-resistant cell lines. Cumulatively, these observations indicate that the presence of the amplified region in a chromosome renders it unstable: chromosomes bearing an amplified region tended to be excluded from cells, and rearrangements were more frequent than in normal chromosomes.
KW - CAD
KW - Chinese hamster cells
KW - DHFR
KW - Gene amplification
KW - Genetic instability
KW - Methotrexate resistance
KW - PALA resistance
UR - http://www.scopus.com/inward/record.url?scp=0024307645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024307645&partnerID=8YFLogxK
U2 - 10.1016/0921-8734(89)90012-X
DO - 10.1016/0921-8734(89)90012-X
M3 - Article
C2 - 2567961
AN - SCOPUS:0024307645
VL - 219
SP - 171
EP - 178
JO - Mutation Research DNAging
JF - Mutation Research DNAging
SN - 0921-8734
IS - 3
ER -