Chromosomal breakage correlates with delayed lethality in normal and ataxia telangiectasia cell lines treated with bleomycin.
Cytogenetic damage and cytotoxicity produced by a range of acute treatments with bleomycin (BLM) were investigated in three B-lymphoblastoid cell lines: EM-OC, PA-AT and CP-NC; established from heterozygous, and homozygous, ataxia telangiectasia (AT) and normal donors, respectively. The following endpoints were studied: (1) the maximum (initial) yields of different classes of chromosomal aberrations (CA) produced in G2-phase; (2) the percentage distributions of cells within bins with different numbers of CA; (3) short-term (0-48 h) viability and proliferation; and (4) (delayed) lethality, as measured by a modified limiting-dilution assay. While only slight losses of short-term viability and proliferation were detectable after standard BLM pulse-treatment at 25 or 100 micrograms/ml (results for latter dose given in parentheses), both regimes subsequently led to intense lethality as follows: CP-NC, 79.3% (95.1%); EM-OC, 90.4% (96.7%) and PA-AT, 98.4% (99.9%). Relative lethality after the respective BLM treatments increased 6.2 x (48.3 x) among PA-AT cells more than in controls-resembling the corresponding ratios for chromosome breaks (csb) of 7.0 x (30.9 x), more than those for chromatid breaks (ctb) of 3.1 x (2.7 x). EM-OC exhibited slightly increased relative lethality after the respective BLM treatments at 2.15 x (1.45), and increased aberration sensitivities for csb of 3.0 x (14.0), while the corresponding ratios for ctb were actually lower at 0.66 x (0.50 x). Significant correlations were observed between lethality and both, the yields of most types of chromosomal aberrations (excepting unambiguous exchanges) and also, the percentages of cells bearing CA.
MacLeod
R A
RA
Department of Human and Animal Cell Cultures, DSMZ-German Collection of Microorganisms, Braunschweig, Germany. rml@gbf.braunschweig.de
Buchheim
T
T
Kaufmann
M
M
Drexler
H G
HG
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001260:Ataxia Telangiectasia / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D001761:Bleomycin / Q000009:adverse effects / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D006720:Homozygote; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D001761:Bleomycin