[The karyotypic variability of Chinese hamster CHLV-79 RJK cells characterized by multiple drug resistance resulting from the amplification of the mdr gene family].
Variability in karyotype structure of Chinese hamster lung V-79 RJK cells and of their six cell sublines, selected for increasing concentrations of ethidium bromide (EB), was investigated in addition to the number of mdr gene copies in cells, both EB sensitive and resistant. It is shown that EB resistant cells exhibit cross-resistance to different drugs resulting from mdr genes amplification. Southern DNA blot hybridization has shown that in Vebr-2 cells (the 1st step of selection) the number of mdr gene copies increased by 10 times, whereas in Vebr-30 cells (the 6th step of selection) the number of mdr gene copies remained the same as in Vebr-2 cells. The level of mdr genes expression in Vebr-30 cells being higher than in Vebr-2 cells. In Vebr-2 cells, homogeneously and differentially stained regions (HSRs) were detected in loci 1p31 and 1q26 of chromosome 1 material (markers Z1 and Z6, respectively). On the following selection steps (prolonged cultivation or increased drug concentration) additional HSRs appeared in chromosome 2 (locus 2qter), in derivatives of chromosome 5 (marker Z7, locus Z7pter) and chromosome X (marker Z2, locus Z2qter). In the course of prolonged cultivation, chromosome 2 and derivatives of chromosomes 1, 2, 5 and X, in which HSRs were found, participated in the formation of new markers resulting from deletions, inversions, insertions and translocations of the chromosomal material. It is supposed that mdr genes amplification in V-79 RJK cells resistant to EB may be regarded as a factor inducing subsequent genome destabilization and eventual progressive changes in the karyotype structure.
Grinchuk
T M
TM
Lipskaia
L A
LA
Artsybasheva
I V
IV
Sorokina
E A
EA
Pan'shina
Iu T
IuT
Ignatova
T N
TN
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004996:Ethidium / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D005784:Gene Amplification / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D007621:Karyotyping; D008168:Lung / Q000166:cytology; D005810:Multigene Family / Q000235:genetics*
D004996:Ethidium
Izmenchivost' kariotipa kletok kitaĭskogo khomiachka CHLV-79 RJK, kharakterizuiushchikhsia mnozhestvennoĭ lekarstvennoĭ ustoĭchivost'iu, obuslovlennaia amplifikatsieĭ genov semeĭstva mdr.