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Relationship between changes in ploidy and stable cellular resistance to hydrogen peroxide
Author(s) -
Spitz Douglas R.,
Mackey Michael A.,
Li Gloria C.,
Elwell James H.,
McCormick Michael L.,
Oberley Larry W.
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041390320
Subject(s) - hydrogen peroxide , chinese hamster ovary cell , catalase , cell culture , microbiology and biotechnology , cell , population , ploidy , biology , chemistry , genetics , biochemistry , enzyme , medicine , gene , environmental health
Stable hydrogen peroxide (H 2 O 2 )‐resistant variants of the Chinese hamster ovary HA‐1 line have been isolated by culturing cells in progressively increasing concentrations of H 2 O 2 (>200 days, in 50–800 μM H 2 O 2 ). Increases in catalase activity in these variant cell lines were shown to correlate with increased H 2 O 2 resistance. Stable (>240 days) H 2 O 2 ‐resistant cell lines, seven quasidiploid (21–22 chromosomes/cell) and six quasitetraploid (40–44 chromosomes/cell) were clonally isolated from the 800 μM adapted H 2 O 2 ‐resistant variants which were heterogeneous with respect to ploidy. The H 2 O 2 dose‐modifying factors (DMFs) were 3, 5, 8, 13, 15, 26, and 27 for the seven quasidiploid cell lines, and 21, 32, 38, 40, 42, and 49 for the six quasitetraploid cell lines. The mean DMF was 14±10 for the former and 37±10 for the latter. Our data show that on the average the quasitetraploid cell lines were significantly more resistant to H 2 O 2 ‐mediated cell killing than the quasidiploid cell lines derived from the same mixed population of 800 μM H 2 O 2 ‐adapted cells. When catalase activities (k units/cell) of the HA‐1 cells and three of the clonally derived cell lines (two quasidiploid and one quasitetraploid) were determined and plotted vs. H 2 O 2 –DMF, a positive linear correlation was obtained (correlation coefficient = 0.99). This result was further confirmed when immunoreactive catalase protein/cell was detected by Western blots. Our data show that chronic exposure of cells to H 2 O 2 stress (800 μM) was accompanied by increases in quasitetraploid cells within the population. Quasitetraploid cell lines derived from this population demonstrated increased stable H 2 O 2 ‐resistance which may be related to stable increases in the expression of catalase.