Two functionally distinct classes of growth arrest states in human prokeratinocytes that regulate clonogenic potential.

Rapidly growing normal human neonatal prokeratinocytes (HPK) cultured in serum-free medium can be induced to undergo either reversible or irreversible growth arrest at distinct cell cycle states. Reversible G1 arrest was induced by culture of low-density cells in human lymphocyte conditioned medium, by culture in high-density stationary phase conditioned medium, and by culture in isoleucine-deficient medium. Irreversible arrest of HPK growth predominantly in G1 was induced by culture in growth factor-deficient medium. Irreversible arrest of HPK growth in G1 and G2 was also induced by culture in suspension in methylcellulose prepared in complete MCDB 153 medium or by culture in serum-containing medium. Finally, the drug razoxane was employed to induce irreversible arrest of HPK in G2. These data establish that there are 2 distinct classes of growth arrest states for HPK and suggest that each arrest mechanism may serve a unique role in the control of keratinocyte differentiation in normal cells. It is also possible that the development of selective defects in either of these processes could be of etiologic significance in certain epidermal disease states.