Do cells of continually renewing populations and those stimulated from quiescence respond similarly to HU and Ara-C?

The cytocidal and cytostatic effects of a single dose of either hydroxyurea (HU) or cytosine arabinoside (Ara-C) have been studied in a variety of tissues, from both rats and mice, by autoradiographic and histological methods. The necrogenic effects of the drugs on DNA-synthesising cells from continually renewing populations have been compared with the effects on cells induced to enter DNA synthesis from a formerly quiescent state. Four models of stimulated proliferation have been studied; the isoprenaline-stimulated salivary glands, the testosterone-stimulated seminal vesicle in the castrate, the regenerating liver after two-thirds partial hepatectomy, and a model of diethylnitrosamine (DEN)-induced hepatocyte proliferation. The time course of the cytokinetic response in each tissue was followed for a period of 24 h after drug treatment. The cytostatic effects of the drugs were similar in all tissues investigated, DNA synthesis being inhibited for a 4- to 5-h period. However, the sensitivity to the lethal effects showed both tissue and species variability.