The kinetics of metaphase arrest in human psoriatic epidermis: an examination of optimal experimental conditions for determining the birth rate

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Abstract
The optimum experimental conditions were investigated for the measurement of the birth-rate in human psoriatic epidermis using the vinca alkaloids vinblastine and vincristine. The dose response characteristics of the 2 drugs were assessed over a 2.5-h collection period; although the dose response characteristics differed between the 2 agents, a dose of 1 .mu.g injected intradermally was considered to be optimal for both. The linearity of metaphase correction was assessed for both agents, taking biopsies for up to 10 h after injection. There was a delay period for up to 1 h which must be avoided during the analysis to prevent an underestimate of the birth rate. Linearity was then demonstrated for up to 4 h after injection. Metaphase degeneration was assessed by isolating a cohort of unlabeled cells in the G2 phase and tracing their fate over the next 10 h. The minimum life of an arrested metaphase was of the order of 4 h, metaphases then degenerated at the rate of approximately 0.4%/h. Metaphase arrest experiments in psoriatic epidermis probably should be confined to 4 h although, if required, correction factors are available to correct for experiments which are lengthened. Flux into DNA synthesis exceeds the flux into mitosis by 4 or 5 times. Several explanations are considered; the most likely explanation involves the death of psoriatic cells in the G2 phase.