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Nuclear DNA content and chromatin texture in multidrug‐resistant human leukemic cell lines
Author(s) -
Dufer Jean,
MillotBroguo Christine,
Hamed Zohra Oum,
LialtaudRoger Francloise,
Joly Philippe,
Desplaces Andrée,
Jardillier JeanClaude
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600116
Subject(s) - chromatin , multiple drug resistance , dna , cell culture , nuclear dna , texture (cosmology) , human cell , cell nucleus , biology , microbiology and biotechnology , genetics , drug resistance , gene , computer science , artificial intelligence , image (mathematics) , mitochondrial dna
Nuclear morphological alterations associated with multidrug resistance (MDR) were evaluated by image cytometry in various human leukemic cell sub‐lines: 3 cell lines with P‐gp‐mediated resistance (CEM‐VLB, HL60/Vinc, K562‐Dox), the non‐Pgp‐mediated MDR HL60/AR leukemic cell line with over‐expres‐sion of MRP, and the at‐MDR CEM‐VMI leukemic cell line with alteration of topoisomerase II. All these MDR cell sub‐lines were obtained by drug selection and were compared with their sensitive counterparts and with the hamster LR73‐R cell line obtained by transfection of mouse mdrl cDNA. All MDR cell sub‐lines obtained by drug selection displayed decreased DNA Feulgen stainability as compared with their respective sensitive parental cell line, a phenomenon not observed in the trans‐fected LR73‐R cells. Nuclear texture analysis on G 0 /G 1 ‐selected cell nuclei revealed 2 types of textural phenotype. The first phenotype was characterized by chromatin decondensation with small but compact chromatin clumps, and was observed in drug‐selected P‐gp‐mediated MDR cells (CEM‐VLB, HL60‐Vinc, K562‐Dox) and in the non‐P‐gp‐mediated MDR HL60/AR cell line. The second phenotype was characterized by a condensed and homogeneous chromatin pattern, and was observed in the at‐MDR CEM‐VMI cell line. LR73‐R cells transfected with mdrl cDNA did not display any significant changes in textural pheno‐type as compared with sensitive LR73 cells, suggesting that P‐gp over‐expression alone cannot account for the cytological modi‐fications observed in MDR cells. These data suggest that multidrug resistance could be associated with specific nuclear morphological changes which appeared to be a consequence of alterations occurring during selection by cytotoxic drugs rather than of P‐gp over‐expression. © 1995 Wiley‐Liss, Inc.