Cell cycle kinetics in normal human skin by in vivo administration of iododeoxyuridine and application of a differentiation marker--implications for cell cycle kinetics in psoriatic skin.
Renewal of epidermal cells is a highly coordinated process in which terminal differentiation balances the proliferative rate in the germinative compartment. Exact quantitative data on cell cycle parameters of normal human epidermis are fragmentary, and do not allow firm conclusions on issues such as cell cycle time, duration of the various cell cycle phases, and the pool sizes of the different cellular populations. As part of a study on bone marrow cell cycle kinetics, 14 lymphoma patients were infused with the thymidine analogue iododeoxyuridine (IdUrd). This provided us with the unique opportunity to study the cell cycle kinetics in normal epidermis obtained from these patients. Single epidermal cell suspensions were prepared from skin, stained with propidium iodide (PI) for relative DNA content, and simultaneously labeled with an anti-IdUrd antibody to detect DNA-synthesizing cells. In parallel samples suprabasal cells were analyzed by labeling with an anti-cytokeratin 10 antibody. Analysis was performed using bivariate flow cytometry. The results showed that 3.5% of the total epidermal cell population was in S-phase. An S-phase duration of 9.7 +/- 0.6 h and a cytokeratin 10-positive pool size of 59.6 +/- 4.6% were obtained. The duration of the G1-phase and the G2M-phase were calculated to be 7.6 +/- 2.0 h and 11.1 +/- 2.0 h, respectively. From these data a total cell cycle time can be calculated of 28.4 h. Combining this data with previous findings we were able to determine a similar cell cycle time of 27.8 h, and pool sizes of the epidermal cells: 30% quiescent (resting, G0) and 10% cycling cells. The implications of these findings for the interpretation of deviations in growth control as found in hyperproliferative skin diseases (e.g. psoriasis) are discussed.
van Erp
P E
PE
Department of Dermatology, University Hospital, Nijmegen, Netherlands. p.vanerp@derma.azn.nl
Boezeman
J B
JB
Brons
P P
PP
D000911:Antibodies, Monoclonal / Q000276:immunology; D002453:Cell Cycle / Q000235:genetics; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage; D015603:Keratinocytes / Q000166:cytology*; D007633:Keratins / Q000276:immunology; D007700:Kinetics; D011419:Propidium; D011565:Psoriasis / Q000473:pathology*; D016196:S Phase / Q000235:genetics; D012867:Skin / Q000166:cytology*
D000911:Antibodies, Monoclonal; D011419:Propidium; D007633:Keratins; D004247:DNA; D007065:Idoxuridine