The Kinetic of Cellular Proliferation in Human Tissues. Determination of Duration of DNA Synthesis Using Double Labeling Autoradiography

Fabrikant, Jacob I.

doi:10.1038/bjc.1970.15

Cited by 23 publications

(2 citation statements)

References 10 publications

(14 reference statements)

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“…Because the nasal vestibular region is the first site ofinteraction of toxic and infectious agents with the respiratory system, the epithehum lining this area may often be subjected to injurious challenges, thus requiring more active regenerative processes. It is also noteworthy that, like the lower gastrointestinal tract, the nasal mucosa is normally colonized by a microbial flora and may be subject to a similarly rapid epithelial cell turnover (12,13) in contrast to the relatively slower turnover occurring in the normally sterile lower respiratory tract (14). Furthermore, parallel observations of human and experimental animal tracheal epithelium revealed that PNP arrays do occur in normal airway epithelium lining the lower respiratory tract, however, they are generally less abundant than in nasal epithelium.…”

Section: Discussionmentioning

confidence: 99%

Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium.

Carson¹,

Collier²,

Knowles³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Observations of freeze-fracture preparations of human nasal epithelium have provided a unique perspective ofthe spatial distribution of epithelial cell cilia unattainable by more conventional ultrastructural techniques. The initial stages of ciliogenesis were characterized ultrastructurally in these preparations by differentiation of the lumenal aspect of the epithelial cell membrane prior to the emergence and maturation of new cilia. Morphometric analyses of the resultant electron micrographs indicate that the development ofan optimal ciliary population during differentiation of ciliated cells may be integral to the adequate functioning of respiratory mucociliary mechanisms. The frequency with which such ciliogenic structures are observed indicates that ciliogenesis is a common feature of the nasal epithelium and suggests that epithelial cell turnover in the nasal cavities is relatively rapid.Classical models of ciliogenesis in the conducting airway epithelial layer have employed experimental animal models to study this aspect ofepithelial cell differentiation. These studies, based on ultrastructural observations of various stages of the developing respiratory system in vivo and in vitro, indicated that beds of cilia emerge from the epithelial cells during a specific stage of embryological development (1-3). It is generally thought that the portion ofcells comprising the mature lumenal border of this pseudostratified columnar epithelium arises through division and differentiation of underlying basal cells into the specialized cell types populating the lumenal border (4). These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development or in response to injury.Recent ultrastructural investigations carried out in this laboratory have demonstrated the occurrence ofciliogenesis in the nasal epithelium ofnormal human subjects. It is clear from these studies that the lumenal membranes of ciliated cells are specifically differentiated prior to the emergence and maturation ofcilia. A developmental sequence in the formation ofthe ciliary necklace (5), a ciliary membrane particle complex, is evident. Initial stages of ciliogenesis are indicated by the formation of prenecklace patches (PNPs) in the lumenal membrane, followed by organization of the particles comprising each patch into the mature ciliary necklace during emergence of the ciliary shaft. Additionally, morphometric studies ofthe nasal epithelium suggest that a critical distribution of cilia occurs on the lumenal border ofciliated cells which may be integral to the maintenance of mucociliary function. MATERIALS AND METHODSInformed consent was obtained from the human volunteers participating in these studies. Samples ofnasal epithelium from the medial surface ofthe inferior turbinate were obtained from normal young men and women by the technique described by Alford...

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Section: Discussionmentioning

confidence: 99%

Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium.

Carson¹,

Collier²,

Knowles³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…These observations also support the experimental design of the present study inasmuch as they suggest that this experimental protocol provides a transient, stable, rapidly incorporated, and detectable pool of available isotope. In another study (Fabrikant, 1970), the period of DNA synthesis in human airway epithelium was determined to be on the order of 10-25 hr. This finding also may provide some insight into the extended period required for ciliated cells to appear with label.…”

Section: Discussionmentioning

confidence: 99%

An autoradiographic assessment of epithelial cell proliferation and post-natal maturation of the tracheal epithelium in infant ferrets

et al. 1999

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The tracheal epithelium of infant ferrets undergoes rapid postnatal maturation over the first month of life to achieve the pseudostratified columnar configuration characteristic of the large airways of other mammals. We have used in vivo pulsing with tritiated thymidine (3 HT) to elicit autoradiographic labeling of cells synthesizing nucleic acids in order to characterize more fully the contribution to development of different cell types comprising the nascent epithelial layer during this period of rapid growth. These studies indicate that two distinct populations of epithelial cells possess proliferative potential and contribute to the establishment of the mature adult epithelial layer. These investigations further confirm the mitotic potential of basal cells during a period of rapid postnatal growth and development of the tracheal epithelial layer. These studies also document the contribution to early airway development by non-ciliated cells, which predominate on the luminal border of the ferret trachea at birth. The temporal and histologic patterns of airway epithelial maturation during post-natal life in the ferret as contained in this study exhibit similarities to those which occur with recovery from injury by infection and irritant exposure in mature airways. Thus, the characterization of epithelial cell compartments having proliferative potential may provide insights into the mechanisms whereby normal airway epithelial organization is established and maintained during development as well as the possible recapitulation of these mechanisms during times of epithelial regeneration following injury.

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Proliferation and differentiation of normal and neoplastic cells in the colon of man

Lipkin

1971

Cancer

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Investigation of proliferate characteristics and of enzymes involved in the metabolism of nucleic acid precursors in colonic cells of man reveal abnormalities in both the replication of the cells and in their differentiation. During migration of normal colonic epithelial cells through the middle third of the colonic crypts, DNA synthesis and mitosis cease as the cells undergo differentiation. However, an early deviation from normal occurs in well‐differentiated colonic epithelial cells of man that continue DNA synthesis and proliferate activity throughout their entire life span. These cells, found in the mucosa of patients who develop neoplastic lesions of the colon, develop an enhanced capacity to proliferate. In neoplastic lesions of increasing size and malignant potential, despite morphological evidence of differentiation, additional abnormalities in nucleic acid enzyme activity develop, and patterns of activity of immature proliferate cells persist. Neoplastic cells of the colon have variable replication rates, with many cells proliferating at near normal, or slower than normal rates. The G2 periodic phase of the proliferate cell cycle was found to be prolonged in villous adenoma and carcinoma cells.

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The Kinetic of Cellular Proliferation in Human Tissues. Determination of Duration of DNA Synthesis Using Double Labeling Autoradiography

Cited by 23 publications

References 10 publications

Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium.

Morphometric aspects of ciliary distribution and ciliogenesis in human nasal epithelium.

An autoradiographic assessment of epithelial cell proliferation and post-natal maturation of the tracheal epithelium in infant ferrets

Proliferation and differentiation of normal and neoplastic cells in the colon of man

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