Quantized generation time in mammalian cells as an expression of the cellular clock.

Abstract

The distribution of possible generation times in mammalian cells does not appear to be continous within the limits of range for each cell type; rather, generation time is quantized in multiples of 3-4 hr. Synchronous cultures of Chinese hamster V79 cells were prepared using manual and automated methods to select and stage mitotic cells. Using synchronous cultures and time-lapse video tape microscopy, it was possible to show that generation times within a population of mitotically selected cells normally disperse in a quantized fashion, with intervals of 3-4 hr occurring between bursts in division. In addition, at temperatures above 37 degrees, V79 cells have a 7.5-8.5 hr modal cell cycle, while at temperatures from 36.5 degrees to 33.5 degrees the modal cell cycle is 11-12 hr long. A survey of the synchrony literature reveals that the tendency to preferred generation times holds between cell lines. The distribution of modal generation times from a variety of different cell types forms a series with a similar interval but with a greater range of values than that observed here for V79 cells. To satisfy the published data and the work presented here, I propose a subcycle, Gq, which has a traverse time equal to the period of the clock. The period appears to be fixed at close to the same value in all mammalian somatic cells. The timekeeping mechanism appears to be temperature compensated, since the time required to traverse Gq is constant at temperatures between 34 degrees and 39 degrees. It is suggested that cell cycle time increases at lower temperatures, lower serum concentration, and high cell densitite because the number of rounds of traverse through Gq increases.