Effects of hydroxyurea on DNA synthesis in hairless mouse epidermis

The effect of 5 mg hydroxyurea (HU) i.p. on epidermal DNA synthesis in female hairless mice was assessed by measuring labelling indices and specific activity after 3HTdR injection, flow cytometry (FCM) and cell sorting of prelabelled basal cells. HU causes an almost immediate block in DNA synthesis lasting until 2-2.5 h. During this time the fraction of cells in S remains stationary, 1.20 of normal. From 2.5 to 12.5 h DNA synthesis is resumed, but in cells recruited from G1 or G0. The HU-blocked cells do not move out of S until after 12.5 h. Hence, from 2.5 to 12.5 h, the fraction of cells in S increases to 2.5 of normal, which means that entry into S is open, but exit is blocked. From 12.5 h flux through S is high. The blocked cells are now released and the fraction of cells in S falls to 0.7 of normal at 24.5 h. At 36.5 h a probable new wave of DNA synthesis is indicated. The results also show that 3HTdR is available for at least 20 min after i.p. injection. The consequences of these results for the interpretation of the effect of HU pretreatment on methylnitrosourea skin carcinogenesis are discussed.