Influence of Myleran on Cell Proliferation in the Lens Epithelium

¹ Ophthalmology Branch, National Institute of Neurological Diseases and Blindness, National Institutes of Health, U. S. Public Health Service, Department of Health, Education, and Welfare Bethesda, Md.

The effect of a single injection of Myleran on mitosis and DNA synthesis in the rat lens epithelium was studied in an effort to explain the cytotoxic and cytostatic action of this alkylating agent. The lens epithelium is well suited to the determination of such effects in their relation to population dynamics and to processes of differentiation and degeneration of cells. The investigation indicates that Myleran acts in the relatively long G₁ period of the cell cycle in a manner which permits the cells to initiate and complete DNA synthesis normally, but prevents their subsequent mitotic division. Affected cells accumulate ina recognizable "Preprophase" state characterized by a bizarre aggregation of chromatin within the nucleus and twice the normal complement of DNA. A portion of the arrested cells undergo nuclear fragmentation and death, and the remainder return to interphase with a tetraploid level of DNA. These cells have a large nucleus and appear to be relatively stable. The Myleran-induced injury seems to affect only a single cell cycle, and the integrity of the population is eventually restored.