A cell kinetic model to explain the time of appearance of skin reaction after X-rays or ultraviolet light irradiation.

Skin reactions to various doses of X-rays (300 and 10 kV) and ultraviolet light (u.v.) have been compared using hairless mice. Two regions of epidermis with widely differing cell kinetics and gross structure have been compared. Little evidence could be found to support the idea that the early phases of the reaction are dependent on cell cycle time. The data can be explained by a model based on the assumption that epidermis contains only a small fraction of clonogenic (stem) cells and this fraction may vary in different epidermal regions. X-rays appear to exert their greatest destructive action on these clonogenic cells while u.v. is more indiscriminate in its action, killing both clonogenic and non-clonogenic cells.     

A comparison of cell replacement in bone marrow,testis and three regions of surface epithelium

What fraction of the proliferative pool cells in epithelial tissues functions as stem cells is still uncertain. Earlier models, based on little or no good evidence, have assumed that this fraction is close to one. Recently there have been developments suggesting that the fraction of stem cells is low, with considerable cell production being attributable to division in short-lived transit proliferative cells. This brings epithelial tissues into line with haematopoiesis and spermatogenesis. This review considers these newer developments and emphasises the similarities between three epithelial regions (skin, tongue and intestine) and bone marrow and testis. Some of the models currently under discussion relate cell position, division polarity, protection of stem genome and hence carcinogenesis. Some of the implications of these models are discussed.     

Apoptosis induced by high- and low-LET radiations

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought thatp53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed inp53-null animals.     

Cell migration velocities in the crypts of the small intestine after cytotoxic insult are not dependent on mitotic activity

The role of mitotic activity in the normal process of intestinal epithelial cell migration was investigated. The movement of [3H]TdR-labelled cells in the crypt-villus column was used to study migration both in the crypts and on the villi. Radiation alone or in conjunction with other cytotoxic agents (hydroxyurea, cyclophosphamide and isopropyl-methane sulphonate) was used to eliminate cell division activity and to decrease crypt cellularity. This was done in order to determine the role of 'mitotic pressure' in driving cell migration. It has been clearly demonstrated in this study that cell migration, both within the crypts and on the villi, can take place in the complete absence of mitotic activity and after a drastic decrease in crypt cellularity. These results add to the continually mounting evidence against the idea that the 'pressure' generated by mitoses within the crypt or indeed in other epithelial regions is responsible for propelling epithelial cells. The data also demonstrate that the migration mechanisms are resistant to cytotoxic exposure.     

Cell Kinetic Studies In the Epidermis of Mouse. Iii. the Percent Labelled Mitosis (Plm) Technique

Full PLM curves have been obtained for four sites in the mouse. the first peaks have been analysed by computer and the duration of the G₂+ M and S phases determined together with their standard deviations. the full curves showed a general similarity for all four sites with no clear second peak. the data are compared with the published data for mouse and human epidermis using the in vivo PLM technique. the timing and shape of the first peak can vary considerably even for one site in mice. Hence, both G₂+ M and S can vary in their durations. Cells labelled at one time of day exhibit different kinetic properties to those labelled at another time of day. the duration of G₂+ M is shortest in dorsum labelled at 03.00 hours (3.2 hr) and longest in tail (up to 7.5 hr). the S-phase is shortest in dorsum (6.3–7.2 hr) and longest in tail or ear (13.3–14.1 hr). There is also a very large standard deviation in tail and foot. There is little general variability when the psoriatic human data are considered, which is surprising. the general variability amongst the data from experimental mice might also be expected amongst humans which might make comparisons between the cell kinetics of normal and diseased skin difficult.     

Intestinal Cell Proliferation. I. A Comprehensive Model of Steady-State Proliferation In the Crypt

Abstract. Cell replacement in the crypt of the murine small intestine has been studied and modelled mathematically under steady-state conditions. A great deal of information is available for this system, e.g. cell cycle times, S phase durations, the rate of daily cell production, the Paneth cell distribution etc. the purpose of the present work was to consider simultaneously as much of these data as possible and to formulate a model based upon the behaviour of individual cells which adequately accounted for them. A simple mathematical representation of the crypt has been developed. This consists of sixteen stem cells per crypt (T_c= 16 hr, T_s= 9 hr), and four subsequent transit cell divisions (T_c= 11 to 12 hr, T_s= 8 hr) before maturation. Experimental data considered to test the modelling were LI and data on the number of vertical runs of similarly labelled cells. All data were obtained from the ileum after 25 μCi [³H]TdR given at 09.00 hours. A number of alternative assumptions have been considered and either accepted or rejected. Two alternative model concepts of cell displacement explain the data equally well. One is dependent upon strong local cell generation age determinance while the other could accommodate any weak local cell displacement process in conjunction with an environmental cut-off determinant at the middle of the crypt. Both models provide new interpretations of the data, e.g. certain rates of lateral cell exchange between neighbouring columns (250 to 350 per crypt per day out of a total of 420 cell divisions per day) can be concluded from run data, while LI data provide information about the mechanisms involved in maintaining a position-related age order in the crypt.