Cell cycle perturbation and cell death after exposure of a human lymphoblastoid cell strain to N-methyl-N'-nitro-N-nitrosoguanidine.
The mechanisms involved in cell death caused by carcinogens that methylate DNA are poorly understood. In this study, the cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in exponentially growing T5-1 human lymphoblastoid cells. MNNG exposure killed cells and inhibited proliferation of the remaining viable cells. Reduction in cell viability, which coincided with the accumulation of cells in the late S phase of the cell cycle, was not apparent until the population had completed one doubling. Fluorescence-activated cell sorting of fluorescein diacetate-stained, MNNG-treated cells into live and dead subpopulations revealed that all cycle phases were well represented in the live fraction, whereas the dead fraction consisted primarily of cells with a sub-G1 DNA content. Thus, cell death after MNNG exposure occurred during the second cell cycle after treatment apparently as a consequence of perturbation of DNA replication and the degradation of nuclear DNA.
Black
K A
KA
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599-7525.
McFarland
R D
RD
Grisham
J W
JW
Smith
G J
GJ
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*
D008769:Methylnitronitrosoguanidine