Measurement of murine epidermal cell proliferation in vivo and applications

A 2H2O labeling method is applied to the measurement of murine epidermal cell (keratinocyte) proliferation in vivo in normal, hypo- and hyper-proliferative conditions. Label incorporation and die-away studies in C57BL/6J mice revealed an epidermis replacement rate of 34--44%/week (half-life of 1.6--2 weeks) and the presence of a non-proliferative subpopulation of epidermal cells (10--15%).; In a carcinogenesis study, topical administration of DMBA and TPA for 3 weeks increased epidermal cell proliferation by 55% in SENCAR mice. 4-week topical application of lunasin, an anti-mitotic soy protein, decreased epidermal cell proliferation modestly, though significantly (16% given alone, 9% given with carcinogens).; The hypo-proliferative response to caloric restriction (CR) was investigated in epidermal, mammary epithelial, and splenic T-cells. In a time course study, 8-week-old female C57BL/6J mice were given a 33% CR regimen (fed 3 times/week) for varying durations. Compared to ad libitum (AL) fed controls, proliferation rates in all tissues were markedly reduced within 2 weeks of CR. In mice fed 95% of AL (C95, fed 3 times/week), cell proliferation was reduced in all tissues so that the differences from 33% CR were only significant at 1 month. In a refeeding study, mice were refed a C95 diet for varying durations after 1 month of 33% CR. Cell proliferation rebounded to a supra-basal rate in all tissues after 2 weeks of refeeding, then normalized after 2 months. The role of intermittent feeding was studied by comparing 33% and 5% CR (both fed intermittently) to animals fed isocalorically either daily or continuously by pellet dispenser. Intermittent feeding had no additive effect on 33% CR but reduced cell proliferation in all tissues at the 95% CR level.; Flaky skin (fsn) mice, a proposed animal psoriasis model, were bred and divided into treatment and non-treatment groups at 3 weeks of age. Treatment mice were given topical applications (50 uL) of glucocorticoid (1 mg/g), calcipotriene (50 ug/g), or a vehicle (cetomacrogol), for 3 weeks. Non-treatment mice were not manipulated. Epidermal cell proliferation was 3- to 5-fold higher in fsn mice than in littermates, but did not differ between glucocorticoid, calcipotriene, vehicle, and non-treatment groups.