Cancer Cell Fitness Is Dynamic.

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.

Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis.

N-methyl-D-aspartate receptors (NMDAR) are glutamate-gated calcium channels named after their artificial agonist. NMDAR are implicated in cell proliferation under normal and pathophysiological conditions. However, the role of NMDAR during mitosis has not yet been explored in individual cells. We found that neurotransmitter-evoked calcium entry via endogenous NMDAR in cortical astrocytes was transient during mitosis. The same occurred in HEK293 cells transfected with the NR1/NR2A subunits of NMDAR. This transient calcium entry during mitosis was due to phosphorylation of the first intracellular loop of NMDAR (S584 of NR1 and S580 of NR2A) by cyclin B/CDK1. Expression of phosphomimetic mutants resulted in transient calcium influx and enhanced NMDAR inactivation independent of the cell cycle phase. Phosphomimetic mutants increased entry of calcium in interphase and generated several alterations during mitosis: increased mitotic index, increased number of cells with lagging chromosomes and fragmentation of pericentriolar material. In summary, by controlling cytosolic calcium, NMDAR modulate mitosis and probably cell differentiation/proliferation. Our results suggest that phosphorylation of NMDAR by cyclin B/CDK1 during mitosis is required to preserve mitotic fidelity. Altering the modulation of the NMDAR by cyclin B/CDK1 may conduct to aneuploidy and cancer.

Surface contraction waves or cell proliferation waves in the presumptive neurectoderm during amphibian gastrulation: Mexican axolotl versus African clawed frog.

This essay represents a critical analysis of the literary data on various types of waves occurring in the amphibian embryos during gastrulation. A surface contraction wave travels through the presumptive neurectoderm during Mexican axolotl gastrulation. This wave coincides temporally and spatially with involution of the inducing chordomesoderm and with the prospective neural plate. By contrast, there is no similar surface contraction wave during African clawed frog gastrulation. However, the clawed frog displays the waves of DNA synthesis and mitosis in the presumptive neurectoderm during gastrulation, whereas no such waves were discovered in axolotl gastrulae. These sets of experimental data are in accordance with the contemporary concept of considerable ontogenetic diversity of the class Amphibia.

Centrosome Abnormalities and Polyploidy in Murine Mammary Carcinomas with Different Degrees of Hormone Responsiveness.

Centrosome amplification leads to aberrant mitosis, giving rise to aneuploidy and it has been associated with poor prognosis in human cancers. This study aimed to evaluate the relationship between polyploidy, centrosome abnormalities, and response to endocrine treatment in progestin-induced mouse mammary carcinomas. We found cells with three or more centrosomes in the polyploid tumors. The endocrine unresponsive tumors showed a higher average number of centrosomes per cell than the responsive tumors. The results suggest an association between polyploidy and centrosome amplification with the resistance to endocrine therapy in this luminal breast cancer model.

De novo lipogenesis at the mitotic exit is used for nuclear envelope reassembly/expansion. Implications for combined chemotherapy.

Mitosis has been traditionally considered a metabolically inactive phase. We have previously shown, however, that extensive alterations in lipids occur as the cells traverse mitosis, including increased de novo fatty acid (FA) and phosphatidylcholine (PtdCho) synthesis and decreased lysophospholipid content. Given the diverse structural and functional properties of these lipids, we sought to study their metabolic fate and their importance for cell cycle completion. Here we show that FA and PtdCho synthesized at the mitotic exit are destined to the nuclear envelope. Importantly, FA and PtdCho synthesis, but not the decrease in lysophospholipid content, are necessary for cell cycle completion beyond G2/M. Moreover, the presence of alternative pathways for PtdCho synthesis renders the cells less sensitive to its inhibition than to the impairment of FA synthesis. FA synthesis, thus, represents a cell cycle-related metabolic vulnerability that could be exploited for combined chemotherapy. We explored the combination of fatty acid synthase (FASN) inhibition with agents that act at different phases of the cell cycle. Our results show that the effect of FASN inhibition may be enhanced under some drug combinations.

SPARC preserves follicular epithelium integrity in insect ovaries.

The importance of juvenile hormone regulating insect oogenesis suggests looking for genes whose expression is regulated by this hormone. SPARC is a calcium-binding glycoprotein that forms part of the extracellular membranes, which in vertebrates participates in bones mineralization or regulating cell proliferation in some cancer types. This large number of functions described for SPARC in different species might be related to the significant differences in its structure observed when comparing different species-groups. Indeed, these structural differences allow characterizing the different clades. In the cockroach Blattella germanica, a SPARC homolog emerged from ovarian transcriptomes that were constructed to find genes responding to juvenile hormone. In insects, SPARC functions have been studied in oogenesis and in embryo development of Drosophila melanogaster. In the present work, using RNAi approaches, novel functions for SPARC in the B. germanica panoistic ovaries are described. We found that depletion of SPARC does not allow to the follicular cells to complete mitosis, resulting in giant follicular cells nuclei and in a great alteration of the ovarian follicle cytoskeleton. The SPARC contribution to B. germanica oogenesis occurs stabilizing the follicular cell program and helping to maintain the nuclear divisions. Moreover, SPARC is necessary to maintain the cytoskeleton of the follicular cells. Any modification of these key processes disables females for oviposition.

Holocentromere identity: from the typical mitotic linear structure to the great plasticity of meiotic holocentromeres.

The centromere is the chromosomal site of kinetochore assembly and is responsible for the correct chromosome segregation during mitosis and meiosis in eukaryotes. Contrary to monocentrics, holocentric chromosomes lack a primary constriction, what is attributed to a kinetochore activity along almost the entire chromosome length during mitosis. This extended centromere structure imposes a problem during meiosis, since sister holocentromeres are not co-oriented during first meiotic division. Thus, regardless of the relatively conserved somatic chromosome structure of holocentrics, during meiosis holocentric chromosomes show different adaptations to deal with this condition. Recent findings in holocentrics have brought back the discussion of the great centromere plasticity of eukaryotes, from the typical CENH3-based holocentromeres to CENH3-less holocentric organisms. Here, we summarize recent and former findings about centromere/kinetochore adaptations shown by holocentric organisms during mitosis and meiosis and discuss how these adaptations are related to the type of meiosis found.

Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life.

The genetic, endocrine, and metabolic mechanisms underlying female reproduction are numerous and sophisticated, displaying complex functional evolution throughout a woman's lifetime. This vital course may be systematized in three subsequent stages: prenatal development of ovaries and germ cells up until in utero arrest of follicular growth and the ensuing interim suspension of gonadal function; onset of reproductive maturity through puberty, with reinitiation of both gonadal and adrenal activity; and adult functionality of the ovarian cycle which permits ovulation, a key event in female fertility, and dictates concurrent modifications in the endometrium and other ovarian hormone-sensitive tissues. Indeed, the ultimate goal of this physiologic progression is to achieve ovulation and offer an adequate environment for the installation of gestation, the consummation of female fertility. Strict regulation of these processes is important, as disruptions at any point in this evolution may equate a myriad of endocrine-metabolic disturbances for women and adverse consequences on offspring both during pregnancy and postpartum. This review offers a summary of pivotal aspects concerning the physiologic course of female reproductive function.

A possible role of Drosophila CTCF in mitotic bookmarking and maintaining chromatin domains during the cell cycle.

BACKGROUND: The CCCTC-binding factor (CTCF) is a highly conserved insulator protein that plays various roles in many cellular processes. CTCF is one of the main architecture proteins in higher eukaryotes, and in combination with other architecture proteins and regulators, also shapes the three-dimensional organization of a genome. Experiments show CTCF partially remains associated with chromatin during mitosis. However, the role of CTCF in the maintenance and propagation of genome architectures throughout the cell cycle remains elusive. RESULTS: We performed a comprehensive bioinformatics analysis on public datasets of Drosophila CTCF (dCTCF). We characterized dCTCF-binding sites according to their occupancy status during the cell cycle, and identified three classes: interphase-mitosis-common (IM), interphase-only (IO) and mitosis-only (MO) sites. Integrated function analysis showed dCTCF-binding sites of different classes might be involved in different biological processes, and IM sites were more conserved and more intensely bound. dCTCF-binding sites of the same class preferentially localized closer to each other, and were highly enriched at chromatin syntenic and topologically associating domains boundaries. CONCLUSIONS: Our results revealed different functions of dCTCF during the cell cycle and suggested that dCTCF might contribute to the establishment of the three-dimensional architecture of the Drosophila genome by maintaining local chromatin compartments throughout the whole cell cycle.

A possible role of Drosophila CTCF in mitotic bookmarking and maintaining chromatin domains during the cell cycle

BACKGROUND: The CCCTC-binding factor (CTCF) is a highly conserved insulator protein that plays various roles in many cellular processes. CTCF is one of the main architecture proteins in higher eukaryotes, and in combination with other architecture proteins and regulators, also shapes the three-dimensional organization of a genome. Experiments show CTCF partially remains associated with chromatin during mitosis. However, the role of CTCF in the maintenance and propagation of genome architectures throughout the cell cycle remains elusive. RESULTS: We performed a comprehensive bioinformatics analysis on public datasets of Drosophila CTCF (dCTCF). We characterized dCTCF-binding sites according to their occupancy status during the cell cycle, and identified three classes: interphase-mitosis-common (IM), interphase-only (IO) and mitosis-only (MO) sites. Integrated function analysis showed dCTCF-binding sites of different classes might be involved in different biological processes, and IM sites were more conserved and more intensely bound. dCTCF-binding sites of the same class preferentially localized closer to each other, and were highly enriched at chromatin syntenic and topologically associating domains boundaries. CONCLUSIONS: Our results revealed different functions of dCTCF during the cell cycle and suggested that dCTCF might contribute to the establishment of the three-dimensional architecture of the Drosophila genome by maintaining local chromatin compartments throughout the whole cell cycle.

Evaluation of liver regeneration with use of diet supplemented with L-arginine.

PURPOSE: To compare controlled liver regeneration in rats submitted to 60% hepatic resection having L-arginine supplemented diet, based on weight changes of the regenerated liver, laboratory parameters of liver function and pathological findings. METHODS: Thirty-six rats were divided into two groups, control and L- arginine. The first received standard chow and saline solution by gavage. The second had supplementation with L- arginine. Animals were killed on postoperative period at 24h, 72h and seven days. For analysis of liver regeneration was used Kwon formula for weight, laboratory tests and mitosis. RESULTS: Weight, showed no benefit with L- arginine supplementation; however, intergroup comparison in the first 24h observed positive effect on supplementation (p=0.008). Alkaline phosphatase was increased in arginine group (p<0.04). The number of mitoses showed no difference between the two groups; however, in the first 24 hours, the supplemented group had higher number of mitoses within the groups (p=0.03). CONCLUSION: Supplementation with L-arginine did not show benefits in liver regeneration; however, supplemented group in the first 24 hours showed benefits over 72 hours and seven days of the evaluation by weight gain and number of mitosis.

Evaluation of liver regeneration with use of diet supplemented with l-arginine

PURPOSE: To compare controlled liver regeneration in rats submitted to 60% hepatic resection having L-arginine supplemented diet, based on weight changes of the regenerated liver, laboratory parameters of liver function and pathological findings. METHODS: Thirty-six rats were divided into two groups, control and L- arginine. The first received standard chow and saline solution by gavage. The second had supplementation with L- arginine. Animals were killed on postoperative period at 24h, 72h and seven days. For analysis of liver regeneration was used Kwon formula for weight, laboratory tests and mitosis. RESULTS: Weight, showed no benefit with L- arginine supplementation; however, intergroup comparison in the first 24h observed positive effect on supplementation (p=0.008). Alkaline phosphatase was increased in arginine group (p<0.04). The number of mitoses showed no difference between the two groups; however, in the first 24 hours, the supplemented group had higher number of mitoses within the groups (p=0.03). CONCLUSION: Supplementation with L-arginine did not show benefits in liver regeneration; however, supplemented group in the first 24 hours showed benefits over 72 hours and seven days of the evaluation by weight gain and number of mitosis. .

La proliferación de los miocitos ventriculares del corazón de mamífero adulto: un fenómeno esporádico pero factible / Proliferation of adult mammalian ventricular cardiomyocytes: A sporadic but feasible phenomenon

La proliferación de los miocitos que forman parte de los ventrículos cardíacos del mamífero adulto ha sido descartada por algunos investigadores con el argumento de que estas células están diferenciadas en forma terminal; sin embargo, este dogma ha sido puesto en duda a partir de los hallazgos de otros investigadores quienes han observado que estos miocitos pueden presentar los procesos necesarios para la proliferación, es decir síntesis de ADN, mitosis y citocinesis, cuando el miocardio se daña en forma experimental con estrategias de tipo farmacológico o quirúrgico, o debido a condiciones patológicas relacionadas con el sistema cardiovascular. Esta revisión integra algunos de los trabajos disponibles en la literatura que han evaluado la síntesis del ADN, mitosis y citocinesis en estas células, en el miocardio dañado, para saber si su proliferación puede ser considerada como un fenómeno factible. La revisión concluye con una reflexión sobre las perspectivas del conocimiento generado en esta área de estudio.

Proliferation of adult mammalian ventricular cardiomyocytes has been ruled out by some researchers, who have argued that these cells are terminally differentiated; however, this dogma has been rejected because other researchers have reported that these cells can present the processes necessary to proliferate, that is, DNA synthesis, mitosis and cytokinesis when the heart is damaged experimentally through pharmacological and surgical strategies or due to pathological conditions concerning the cardiovascular system. This review integrates some of the available works in the literature evaluating the DNA synthesis, mitosis and cytokinesis in these myocytes, when the myocardium is damaged, with the purpose of knowing if their proliferation can be considered as a feasible phenomenon. The review is concluded with a reflection about the perspectives of the knowledge generated in this area.

[Proliferation of adult mammalian ventricular cardiomyocytes: a sporadic but feasible phenomenon]. / La proliferación de los miocitos ventriculares del corazón de mamífero adulto: un fenómeno esporádico pero factible.

Proliferation of adult mammalian ventricular cardiomyocytes has been ruled out by some researchers, who have argued that these cells are terminally differentiated; however, this dogma has been rejected because other researchers have reported that these cells can present the processes necessary to proliferate, that is, DNA synthesis, mitosis and cytokinesis when the heart is damaged experimentally through pharmacological and surgical strategies or due to pathological conditions concerning the cardiovascular system. This review integrates some of the available works in the literature evaluating the DNA synthesis, mitosis and cytokinesis in these myocytes, when the myocardium is damaged, with the purpose of knowing if their proliferation can be considered as a feasible phenomenon. The review is concluded with a reflection about the perspectives of the knowledge generated in this area.

The ileum positively regulates hepatic regeneration in rats.

PURPOSE: To test the hypothesis that liver regeneration after partial hepatectomy can be influenced by the ileum. METHODS: Eighteen Wistar rats were distributed into groups of six animals: 1 - ileum resection+ hepatectomy 2/3; 2 - hepatectomy 2/3, and 3 - sham. Anesthesia with ketamine and xylazine i.p., aseptic technique, analgesia with meperidine (10mg/kg s.c.). On day 6, serum ALT, AST, alkaline phosphatase (AP) and albumin were measured. Liver regeneration and hepatocyte mitosis were quantified. Statistical analysis with ANOVA and Tukey tests, with significance p<0.05. RESULTS: In group hepatectomy+ileal resection, ALT, AST and AP were 180.6±24.9, 58.6±3.1 and 254.6±46.6 respectively. They were significantly higher than in the hepatectomy group, whose values were 126.0±16.5, 44.1±3.9 and 163.5±8.6, respectively (p<0.001). Albumin levels were not significantly different among groups. Liver regeneration in hepatectomy group (94.17%) was statistically higher (p<0.001) than in ileal resection+hepatectomy group (55.96%). In the latter group the mitosis of hepatocytes were significantly less frequent than in the hepatectomy group. CONCLUSION: The data confirm that the ileum positively influence on liver regeneration in rats undergoing hepatectomy.

Developmental expression and role of Kinesin Eg5 during Xenopus laevis embryogenesis.

BACKGROUND: The neural crest is a transient multipotent migratory cell population unique to vertebrates. These cells undergo an epithelial-to-mesenchymal transition and migrate extensively through the embryo. They differentiate into numerous diverse derivatives including the peripheral nervous system, melanocytes,and craniofacial cartilages. The development of the neural crest is mediated by complex interactions of multiple signals and transcription factors. The kinesin Eg5 is a plus end-directed microtubule-based motor protein that is essential for bipolar spindle formation during mitosis and meiosis, axon growth, and mammal embryonic development. RESULTS: We analyzed in detail the expression pattern of eg5 and established that it is expressed at the prospective neural fold, in the premigratory and migratory neural crest. Functional analysis revealed that in Xenopus, early embryogenesis eg5 function is required during neural crest induction, specification, and maintenance. eg5 is also required during neural crest migration and for derivatives formation. Moreover, we demonstrated a hierarchical relationship with the Indian Hedgehog signaling pathway. CONCLUSIONS: Our results show that eg5 is essential for the specification and maintenance of neural crest progenitors during Xenopus early embryogenesis rather than cell proliferation and survival.

Control of oocyte maturation

Oocyte maturation is a complex process involving nuclear and cytoplasmic maturation. The nuclear maturation is a chromosomal segregation and the cytoplasmic maturation involves the reorganization of the cytoplasmic organelles, mRNA transcription and storage of proteins to be used during fertilization and early embryo development. The mechanism of oocyte maturation in vivo and in vitro still are not totally understood. However it is generally accepted that the second messenger cyclic adenosine monophosphate (cAMP) plays a critical role in the maintenance of meiotic blockage of mammalian oocytes. A relative increase in the level of cAMP within the oocyte is essential for maintaining meiosis block, while a decrease in cAMP oocyte concentration allows the resumption of meiosis. The oocyte cAMP concentration is regulated by a balance of two types of enzymes: adenylate cyclase (AC) and phosphodiesterases (PDEs), which are responsible for the synthesis and degradation of cAMP, respectively. After being synthesized by AC in cumulus cells, cAMP are transferred to the oocyte through gap junctions. Thus, specific subtypes PDEs are able to inhibit or attenuate the spontaneous meiotic maturation of oocytes with PDE4 primarily involved in the metabolism of cAMP in granulosa cells and PDE3 in the oocyte. Although the immature oocytes can resume meiosis in vitro, after being removed from antral follicles, cytoplasmic maturation seems to occur asynchronously with nuclear maturation. Therefore, knowledge of the oocyte maturation process is fundamental for the development of methodologies to increase the success of in vitro embryo production and to develop treatments for various forms of infertility. This review will present current knowledge about the maintenance of the oocyte in prophase arrest, and the resumption of meiosis during oocyte maturation, focusing mainly on the changes that take place in the oocyte.

Control of oocyte maturation

Oocyte maturation is a complex process involving nuclear and cytoplasmic maturation. The nuclear maturation is a chromosomal segregation and the cytoplasmic maturation involves the reorganization of the cytoplasmic organelles, mRNA transcription and storage of proteins to be used during fertilization and early embryo development. The mechanism of oocyte maturation in vivo and in vitro still are not totally understood. However it is generally accepted that the second messenger cyclic adenosine monophosphate (cAMP) plays a critical role in the maintenance of meiotic blockage of mammalian oocytes. A relative increase in the level of cAMP within the oocyte is essential for maintaining meiosis block, while a decrease in cAMP oocyte concentration allows the resumption of meiosis. The oocyte cAMP concentration is regulated by a balance of two types of enzymes: adenylate cyclase (AC) and phosphodiesterases (PDEs), which are responsible for the synthesis and degradation of cAMP, respectively. After being synthesized by AC in cumulus cells, cAMP are transferred to the oocyte through gap junctions. Thus, specific subtypes PDEs are able to inhibit or attenuate the spontaneous meiotic maturation of oocytes with PDE4 primarily involved in the metabolism of cAMP in granulosa cells and PDE3 in the oocyte. Although the immature oocytes can resume meiosis in vitro, after being removed from antral follicles, cytoplasmic maturation seems to occur asynchronously with nuclear maturation. Therefore, knowledge of the oocyte maturation process is fundamental for the development of methodologies to increase the success of in vitro embryo production and to develop treatments for various forms of infertility. This review will present current knowledge about the maintenance of the oocyte in prophase arrest, and the resumption of meiosis during oocyte maturation, focusing mainly on the changes that take place in the oocyte. (AU)

The jejunoileal bypass provokes morphological changes in the large intestine? An experimental study in rats.

PURPOSE: To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation after continued administration of sodium nitrite and vitamin C to different groups. METHODS: Eighty male Wistar rats were employed and separated into 12 groups. In the control group (20 rats): five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the sham group (20 rats), the animals were anesthetized and underwent midline laparotomy and only intestinal manipulation was performed: five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the operated group 40 rats underwent a jejunoileal bypass surgery: ten animals ingested only water; ten animals received vitamin C; ten animals received sodium nitrite and ten received sodium nitrite + vitamin C. The mean weight of the animals was measured weekly. The large intestine was subdivided into cecum (S1), ascending colon (S(2)), transverse colon (S(3)), descending colon (S(4)) and rectum (S(5)) for histopathological analysis and mitotic counts. The statistical analysis was used to compare the mitotic indices. The level of significance was 5%. RESULTS: The mean of all the segments indicates that the sodium nitrite+vitamin C group obtained the lowest mitotic index compared to the other treatments in the control group. The segments S(1) and S(2) showed a statistical difference with the vitamin C treatment: a higher mitotic index and better preservation of the mucosa in the operated group. In the sham group the main statistical difference occurred only in the sodium nitrite+vitamin C group between the means of the segments. CONCLUSIONS: The comparison of all the colonic segments of the various groups revealed a lower mitotic index in the animals treated with sodium nitrite+vitamin C. In addition, it was found that vitamin C did not present a statistically significant inhibiting effect on the preservation of the mucosa and the mitotic index.

The jejunoileal bypass provokes morphological changes in the large intestine? An experimental study in rats / A derivação jejuno-ileal provoca alterações morfológicas no intestino grosso? Estudo experimental em ratos

PURPOSE: To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation after continued administration of sodium nitrite and vitamin C to different groups. METHODS: Eighty male Wistar rats were employed and separated into 12 groups. In the control group (20 rats): five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the sham group (20 rats), the animals were anesthetized and underwent midline laparotomy and only intestinal manipulation was performed: five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the operated group 40 rats underwent a jejunoileal bypass surgery: ten animals ingested only water; ten animals received vitamin C; ten animals received sodium nitrite and ten received sodium nitrite + vitamin C. The mean weight of the animals was measured weekly. The large intestine was subdivided into cecum (S1), ascending colon (S2), transverse colon (S3), descending colon (S4) and rectum (S5) for histopathological analysis and mitotic counts. The statistical analysis was used to compare the mitotic indices. The level of significance was 5%. RESULTS: The mean of all the segments indicates that the sodium nitrite+vitamin C group obtained the lowest mitotic index compared to the other treatments in the control group. The segments S1 and S2 showed a statistical difference with the vitamin C treatment: a higher mitotic index and better preservation of the mucosa in the operated group. In the sham group the main statistical difference occurred only in the sodium nitrite+vitamin C group between the means of the segments. CONCLUSIONS: The comparison of all the colonic segments of the various groups revealed a lower mitotic index in the animals treated with sodium nitrite+vitamin C. In addition, it was found that vitamin C did not present a statistically significant inhibiting effect on the preservation of the mucosa and the mitotic index.

OBJETIVO: Analisar as alterações histopatológicas caracterizada pelo índice mitótico na mucosa do intestino grosso em ratos Wistar submetidos a operação de bypass jejunoileal após a administração continuada de nitrito de sódio e vitamina C para diferentes grupos. MÉTODOS: Oitenta ratos Wistar foram utilizados e separados em 12 grupos. No grupo controle (20 ratos): cinco animais ingeriram apenas água; cinco animais receberam vitamina C, cinco animais receberam nitrito de sódio e cinco receberam nitrito de sódio + vitamina C. No grupo sham (20 ratos), os animais foram anestesiados e submetidos a laparotomia mediana e só a manipulação intestinal foi realizada: cinco animais ingeriram apenas água; cinco animais receberam vitamina C, cinco animais receberam nitrito de sódio e cinco receberam nitrito de sódio + vitamina C. No grupo operado 40 ratos foram submetidos a uma cirurgia de bypass jejunoileal: dez animais ingeridos apenas água; dez animais receberam vitamina C, dez animais receberam nitrito de sódio e dez nitrito de sódio + vitamina C. O peso médio dos animais foi medido semanalmente. O intestino grosso foi subdividido em ceco (S1), cólon ascendente (S2), cólon transverso (S3), cólon descendente (S4) e reto (S5) para análise histopatológica e contagem das mitoses. A análise estatística foi utilizado para comparar os índices mitóticos. O nível de significância foi de 5%. RESULTADOS: A média de todos os segmentos indica que o grupo que ingeriu nitrito de sódio + vitamina C obteve o menor índice mitótico em relação aos demais tratamentos no grupo controle. Os segmentos S1 e S2 mostraram uma diferença estatística com a vitamina C de tratamento: um maior índice mitótico e melhor preservação da mucosa no grupo operado. No grupo sham a principal diferença estatística ocorreu apenas no grupo que ingeriu nitrito de sódio + vitamina C entre as médias dos segmentos. CONCLUSÕES: A comparação de todos os segmentos do colon dos vários grupos revelaram um menor índice de mitose nos animais tratados com nitrito de sódio + vitamina C. Além disso, a vitamina C não apresentou efeito inibidor, estatísticamente significativo, na preservação da mucosa e do índice de mitoses.