Morphometric and Allometric Study of the Mouse Exocrine Pancreas Growth During the Postnatal Life

Taga, Rumio; Bispo, Luciano Bonatelli; Bordin, Rodrigo Ayres; Hassunuma, Renato Massaharu

doi:10.2535/ofaj1936.74.6_271

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Our observations demonstrate that, although no structural modification occurs in pancreatic acinar cells of mice fed on GM soybean, quantitative changes of some cellular constituents take place in comparison with control animals. Cellular, nuclear and cytoplasmic areas as well as N/C ratio change in relation to the age only, probably because of the postnatal development of pancreatic acinar cells (Taga et al. 1998).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

Malatesta¹,

Caporaloni

Rossi

et al. 2002

Journal of Anatomy

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No direct evidence that genetically modified (GM) food may represent a possible danger for health has been reported so far; however, the scientific literature in this field is quite poor. Therefore, we investigated the possible effects of a diet containing GM soybean on mouse exocrine pancreas by means of ultrastructural, morphometrical and immunocytochemical analyses. Our observations demonstrate that, although no structural modification occurs in pancreatic acinar cells of mice fed on GM soybean, quantitative changes of some cellular constituents take place in comparison to control animals. In particular, a diet containing significant amount of GM food seems to influence the zymogen synthesis and processing.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

Malatesta¹,

Caporaloni

Rossi

et al. 2002

Journal of Anatomy

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“…5c) (25,26), which raises the possibility that the increase in the number of foci is because of the increase in surface area of pancreata (Fig. 5c).…”

Section: Flow Cytometry Analysis Of Hr Events In Adult Pancreaticmentioning

confidence: 99%

Age-dependent accumulation of recombinant cells in the mouse pancreas revealed byin situfluorescence imaging

Wiktor-Brown

Hendricks²,

Olipitz³

et al. 2006

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

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Mitotic homologous recombination (HR) is critical for the repair of double-strand breaks, and conditions that stimulate HR are associated with an increased risk of deleterious sequence rearrangements that can promote cancer. Because of the difficulty of assessing HR in mammals, little is known about HR activity in mammalian tissues or about the effects of cancer risk factors on HR in vivo. To study HR in vivo, we have used fluorescent yellow direct repeat mice, in which an HR event at a transgene yields a fluorescent phenotype. Results show that HR is an active pathway in the pancreas throughout life, that HR is induced in vivo by exposure to a cancer chemotherapeutic agent, and that recombinant cells accumulate with age in pancreatic tissue. Furthermore, we developed an in situ imaging approach that reveals an increase in both the frequency and the sizes of isolated recombinant cell clusters with age, indicating that both de novo recombination events and clonal expansion contribute to the accumulation of recombinant cells with age. This work demonstrates that aging and exposure to a cancer chemotherapeutic agent increase the frequency of recombinant cells in the pancreas, and it also provides a rapid method for revealing additional factors that modulate HR and clonal expansion in vivo.aging ͉ homologous recombination ͉ mutation ͉ chemotherapy C ells are constantly exposed to endogenous and exogenous DNA-damaging agents that can lead to double-strand breaks, either by causing breaks in both strands of DNA or by causing replication fork breakdown (1). Homologous recombination (HR) is critical for repairing double-strand breaks in mammalian cells. By using homologous DNA sequences present on the sister chromatid or homologous chromosome, damage can be repaired accurately without loss of sequence information (2, 3). Thus, the frequency of HR reflects both the levels of double-strand breaks and the ability of cells to use HR during DNA repair.Although HR is generally error-free, recombination between misaligned sequences can cause insertions, deletions, and translocations. Furthermore, recombination between homologous chromosomes can lead to loss of heterozygosity (4), and HR has been estimated to be the underlying cause of loss of heterozygosity 25-80% of the time in mammalian cells (e.g., see ref. 5). Germ-line mutations in genes that modulate the frequency of HR are associated with an increased risk of cancer. For example, inherited mutations in the HR helicases BLM and WRN lead to increased rates of HR (6, 7) and increase the risk of cancer (8).Whereas too much HR can be problematic, too little HR can also destabilize the genome, possibly as a result of nonhomologous end-joining of DNA ends created at broken replication forks (4, 9). In the pancreas, inherited mutations in BRCA1 (8), BRCA2 (10), and FANCC (11) increase the risk of pancreatic cancer, and loss of function of these genes suppresses HR (12-14), causing an increased frequency of tumorigenic sequence rearrangements (15,16). Although these findings sug...

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“…More specifically, since HR at specific locus is a rare event, the frequency of recombinant cells in the pancreas is approximately five cells per million ( Wiktor-Brown et al 2006). The pancreas of adult mouse contains approximately 3!10 7 cells (Taga et al 1998) and has a size of approximately 2 cm by 1 cm by 0.05 cm when it was placed on a slide glass. If there were approximately 50 recombinant foci in one pancreas, it would take approximately 8.5 days (210 hours) for a typical, non-video-rate, TPM to image an entire pancreas, assuming this microscope can cover a field of view (FOV ) of 240!240 mm 2 at one frame s K1 .…”

Section: Site Selective Tissue Cytometrymentioning

confidence: 99%

Quantitative morphometric measurements using site selective image cytometry of intact tissue

Kwon

Nam

Wiktor-Brown

et al. 2008

J. R. Soc. Interface.

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Site selective two-photon tissue image cytometry has previously been successfully applied to measure the number of rare cells in three-dimensional tissue specimens up to cubic millimetres in size. However, the extension of this approach for high-throughput quantification of cellular morphological states has not been demonstrated. In this paper, we report the use of siteselective tissue image cytometry for the study of homologous recombination (HR) events during cell division in the pancreas of transgenic mice. Since HRs are rare events, recombinant cells distribute sparsely inside the organ. A detailed measurement throughout the whole tissue is thus not practical. Instead, the site selective two-photon tissue cytometer incorporates a low magnification, wide field, one-photon imaging subsystem that rapidly identifies regions of interest containing recombinant cell clusters. Subsequently, high-resolution three-dimensional assays based on two-photon microscopy can be performed only in these regions of interest. We further show that three-dimensional morphology extraction algorithms can be used to analyse the resultant high-resolution two-photon image stacks providing information not only on the frequency and the distribution of these recombinant cell clusters and their constituent cells, but also on their morphology.

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Morphometric and Allometric Study of the Mouse Exocrine Pancreas Growth During the Postnatal Life

Cited by 8 publications

References 16 publications

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

Ultrastructural analysis of pancreatic acinar cells from mice fed on genetically modified soybean

Age-dependent accumulation of recombinant cells in the mouse pancreas revealed byin situfluorescence imaging

Quantitative morphometric measurements using site selective image cytometry of intact tissue

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