Effect of hydroxyurea on differentiation of mitotically inactive olfactory receptor cells in the frog.

Hydroxyurea is a widely used mitotic suppressant, but its action on nondividing cells remains largely unknown. This is a study of the effect of the drug on the development of newly generated, mitotically inactive olfactory receptor cells in adult frogs. To obtain olfactory epithelia consisting of newly generated cells, the original olfactory epithelia in a group of animals were ablated by irrigation of their nasal cavities with a solution of zinc sulfate in distilled water. The new epithelial cells were then allowed to generate over a period of 10 days. The hydroxyurea treatment was carried out by delivering a 50 mM concentration of the drug in Ringer's solution into the frogs' nasal cavities at a flow rate of 0.40 ml/day continuously for 24 days. Such treatment was capable of suppressing mitotic activity in olfactory epithelia. Morphological and electrophysiological observations of olfactory receptor cells, which were developing during hydroxyurea treatment, did not reveal any notable differences in comparison with olfactory receptor cells in control epithelia treated only with Ringer's solution. Thus the prolonged treatment of olfactory epithelia with hydroxyurea employed in this study, while suppressing mitotic activity in these tissues, did not significantly affect the differentiation of young postmitotic receptor cells.