Study of Mechanisms of Radiation-Induced Reproductive Death of Mammalian Cells in Culture: Estimation of Stage at Cell Death and Biological Description of Processes Leading to Cell Death

Abstract

Lethally irradiated cells undergo one of two types of death, the so-called death or interphase death (1, 2). Since L5178Y cells exposed to moderately large doses of ionizing radiation have been shown to undergo reproductive death (3) (as do most cultured mammalian cells), this cell line appears to be suitable for the studies of the mechanisms leading to this type of death. As the first step in such a study, we believed that there was a great need for a better and more complete description of the process of reproductive death than those currently available (4-9). As early as 1937, Tansley, Spear, and Gliicksmann observed that, in irradiated rat retina, the peak of cell degeneration was always preceded by the peak of mitosis. This finding was extended to other cell systems, mainly by Spear and his colleagues (4-7). Lea interpreted this as suggesting that the degenerative process leading to cell death begins at mitotic division (1). In spite of the importance of such a statement, no serious effort has been made to elucidate this phenomenon. With the new concept of life cycle of cells introduced by Howard and Pelc (10) and Lajtha et al. (11), it has become obvious that the process of reproductive death of irradiated cells can be studied in terms of biological events occurring throughout the life cycle. In the present paper, we have placed special emphasis on the question: At what stage of its life cycle does an irradiated cell die? The answer to this basic question would seem essential for the understanding of the exact biological mechanisms leading to reproductive cell death.