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. 1989 Jan;134(1):53–61.

Cell cycle perturbation and cell death after exposure of a human lymphoblastoid cell strain to N-methyl-N'-nitro-N-nitrosoguanidine.

K A Black 1, R D McFarland 1, J W Grisham 1, G J Smith 1
PMCID: PMC1879564  PMID: 2913827

Abstract

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.

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Selected References

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