Reversal of colchicine-induced mitotic arrest in Chinese hamster cells with a colchicine-specific monoclonal antibody.
The ability of a high-affinity colchicine-binding monoclonal antibody to reverse the effects of colchicine on Chinese hamster ovary cells was investigated. Using flow cytometry, a complete mitotic blockade was demonstrated after 16 hours with 2.5 x 10(-7) mol/l (molar) colchicine. Colchicine-induced changes were reversible when equimolar antibody was added simultaneously with or up to 6 hours after colchicine. With further delay in addition of antibody, a progressive irreversible increase in mitotic blockade and increase in mean cell size was observed. Prolonged colchicine exposure, without antibody reversal, led to polyploidy and structural chromosome breakage. Early antibody reversal restored cells to the diploid state, whereas delayed reversal resulted in a time-dependent increase in polyploidy. Colchicine-induced polyploidy and chromosomal aberrations may be the basis for both colchicine toxicity and the time-dependent increase in irreversibility of colchicine effects.
Rouan
S K
SK
Department of Pharmaceutics, University of Rhode Island, Kingston.
Otterness
I G
IG
Cunningham
A C
AC
Holden
H E
HE
Rhodes
C T
CT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002869:Chromosome Aberrations; D003078:Colchicine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000633:toxicity; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D008938:Mitosis / Q000187:drug effects*; D011003:Ploidies; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003078:Colchicine