Cell-cycle distribution of pancreatic cells from rats with acute pancreatitis induced by bile-pancreatic obstruction

Dios, Isabel De; Uruñuela, Aránzazu; MaPinto, Rosa; Órfão, Alberto; Manso, Manuel A.

doi:10.1007/s004410000194

Cited by 11 publications

(11 citation statements)

References 30 publications

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“…In fact, the morphological study revealed extensive cell injury in the different pancreatic sections at these stages. As has been reported previously [17][18][19]37,38] in this model of pancreatitis, apoptosis was also observed, which is a type of cell death associated with increased intracellular Ca# + concentration [39].…”

Section: Discussionsupporting

confidence: 84%

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Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat

et al. 2002

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Current evidence suggests that alterations within acinar cells are responsible for the development of acute pancreatitis. After inducing acute pancreatitis in rats by pancreatic duct obstruction, we analysed, using flow cytometry, the progressive changes in cytosolic Ca2+ concentrations in individual acinar cells from the earliest stages to 48 h after obstruction to investigate whether parallel alterations in the homoeostasis of Ca2+ could be defined in the different acinar cells throughout the evolution of pancreatitis. Morphological alterations of the pancreas, related to the severity of the disease at different stages, were observed by electron microscopy. Hyperamylasaemia and progressively more severe alterations, such as vacuolization, dilatation of endoplasmic reticulum, accumulation of zymogen granules and reorientation towards basolateral membrane, were observed during the first 12 h after pancreatic obstruction. A significant increase in cytosolic Ca2+ concentration was measured at these stages in a particular type of acinar cells (R1) differentiated by flow cytometry with low forward scatter (FSC), whereas another representative group of cells (R2) with higher FSC values were able to maintain resting cytosolic Ca2+ concentrations up to 24 h after obstruction. Longer periods of pancreatic duct obstruction induced disturbances in Ca2+ homoeostasis in all acinar cells. A similar increase in cytosolic Ca2+ load was reached in both R1 and R2 cells when acute pancreatitis was completely developed. In conclusion, the homoeostasis of Ca2+ in acinar cells is asynchronously impaired during the development of acute pancreatitis; cells with higher FSC (R2) appear to be more resistant than R1 cells.

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Section: Discussionsupporting

confidence: 84%

“…Two different subsets of acinar cells have been reported by us in previous studies [17][18][19] that were termed R1 and R2. They can be clearly differentiated on the basis of light scatter properties ; R1 cells display lower forward and side scatter than R2 cells.…”

Section: Introductionmentioning

confidence: 99%

Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat

et al. 2002

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“…HR activity is most active during S phase and late S/G2 [45], however, in the pancreas, the vast majority of cells are not in S phase [46]. To explore the effect of p53 status on HR in rapidly dividing cells, we created primary ear fibroblast cultures from Fydr y/y ; p53 +/+ and Fydr y/y ; p53 −/− mice, and analyzed genome-wide HR events using the sister chromatid exchange (SCE) assay [47].…”

Section: Resultsmentioning

confidence: 99%

p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination

Wiktor-Brown¹,

Sukup-Jackson²,

Fakhraldeen³

et al. 2011

DNA Repair

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The tumor suppressor p53 is a transcription factor whose function is critical for maintaining genomic stability in mammalian cells. In response to DNA damage, p53 initiates a signaling cascade that results in cell cycle arrest, DNA repair or, if the damage is severe, programmed cell death. In addition, p53 interacts with repair proteins involved in homologous recombination. Mitotic homologous recombination (HR) plays an essential role in the repair of double-strand breaks (DSBs) and broken replication forks. Loss of function of either p53 or HR leads to an increased risk of cancer. Given the importance of both p53 and HR in maintaining genomic integrity, we analyzed the effect of p53 on HR in vivo using Fluorescent Yellow Direct Repeat (FYDR) mice as well as with the sister chromatid exchange (SCE) assay. FYDR mice carry a direct repeat substrate in which an HR event can yield a fluorescent phenotype. Here, we show that p53 status does not significantly affect spontaneous HR in adult pancreatic cells in vivo or in primary fibroblasts in vitro when assessed using the FYDR substrate and SCEs. In addition, primary fibroblasts from p53 null mice do not show increased susceptibility to DNA damage-induced HR when challenged with mitomycin C. Taken together, the FYDR direct repeat assay and SCE analysis indicate that, for some tissues and cell types, p53 status does not greatly impact HR.

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“…For these studies, a comparison of pancreas and skin shows that while cells within the adult pancreas exhibit extremely low levels of proliferation (~1% of cells are in S phase [60]) and persist for long periods of time (turnover time of ~250-500 days [59]), cells within the skin have higher proliferation rates and relatively short persistence times (turnover time of ~7-60 days [59]). Despite the seemingly low level of proliferation in the pancreas, a dramatic increase in recombinant cell frequency is observed with age.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific differences in the accumulation of sequence rearrangements with age

et al. 2008

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Mitotic homologous recombination (HR) is a critical pathway for the accurate repair of DNA double strand breaks (DSBs) and broken replication forks. While generally error-free, HR can occur between misaligned sequences, resulting in deleterious sequence rearrangements that can contribute to cancer and aging. To learn more about the extent to which HR occurs in different tissues during the aging process, we used Fluorescent Yellow Direct Repeat (FYDR) mice in which an HR event in a transgene yields a fluorescent phenotype. Here, we show tissue-specific differences in the accumulation of recombinant cells with age. Unlike pancreas, which shows a dramatic 23-fold increase in recombinant cell frequency with age, skin shows no increase in vivo. In vitro studies indicate that juvenile and aged primary fibroblasts are similarly able to undergo HR in response to endogenous and exogenous DNA damage. Therefore, the lack of recombinant cell accumulation in the skin is most likely not due to an inability to undergo de novo HR events. We propose that tissue-specific differences in the accumulation of recombinant cells with age result from differences in the ability of recombinant cells to persist and clonally expand within tissues.

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Cell-cycle distribution of pancreatic cells from rats with acute pancreatitis induced by bile-pancreatic obstruction

Cited by 11 publications

References 30 publications

Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat

Asynchronous impairment of calcium homoeostasis in different acinar cells after pancreatic duct obstruction in rat

p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination

Tissue-specific differences in the accumulation of sequence rearrangements with age

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