Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma

Almeida, Thais Oliveira; Leitão, Regina C; Andrade, Joyce D; Beçak, Willy; Carrilho, Flair José; Sonohara, Shigueko

doi:10.1016/j.cancergencyto.2003.08.001

Cited by 27 publications

(16 citation statements)

References 31 publications

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“…This results in formation of regenerative hepatocytes nodules. Therefore, the increase in hepatocytes' nuclei seen in this study might be due to the above-mentioned triggering regenerative response (26).…”

Section: Discussionmentioning

confidence: 68%

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Rafati¹,

Hoseini²,

Babai³

et al. 2015

JFN

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Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P＜0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P＜0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P＜0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P＜0.03).

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Section: Discussionmentioning

confidence: 68%

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Rafati¹,

Hoseini²,

Babai³

et al. 2015

JFN

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“…19 Hepatocytes with pyknotic nuclei and those that overlapped were not assessed for micronuclei count. The micronuclei index was defined as the number of micronuclei per 3000 hepatocytes.…”

Section: Micronuclei Studymentioning

confidence: 99%

“…12 The micronucleus, an indicator of chromosome damage, arises from chromosome fragments or whole chromosomes in the anaphase and telophase stages and manifest as small nuclei in the cytoplasm of interphase cells, and therefore are regarded as indicators of genomic instability in dividing cells. [14][15][16][17][18][19] In rodent models of experimental hepatocarcinogenesis, the number of micronuclei increased with progression of hepatocarcinogenesis as measured by genetic alterations. 16,17 Micronucleated hepatocytes have also been reported to be significantly more frequent in hepatocellular carcinomas compared with cirrhotic regenerative nodules and normal hepatic parenchyma.…”

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confidence: 99%

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Chromosomal instability, telomere shortening, and inactivation of p21WAF1/CIP1 in dysplastic nodules of hepatitis B virus-associated multistep hepatocarcinogenesis

Lee

Yoo

et al. 2009

Modern Pathology

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Systemic analysis for chromosomal instability and inactivation of cell cycle checkpoints are scarce during hepatocarcinogenesis. We studied 24 patients with chronic B viral cirrhosis including 30 cirrhotic regenerative nodules, 35 low-grade dysplastic nodules, 15 high-grade dysplastic nodules, 7 dysplastic nodules with hepatocellular carcinoma foci, and 18 hepatocellular carcinomas. Eight normal livers were studied as the control group. Telomere length and micronuclei were detected by Southern blot and Feulgen-fast green dyeing technique, respectively, and p21 WAF1/CIP1 expression was studied by immunohistochemistry. Micronuclei 41 per 3000 hepatocytes were found in 17% of low-grade dysplastic nodules, 87% of high-grade dysplastic nodules, and 100% of high-grade dysplastic nodules with hepatocellular carcinoma foci and hepatocellular carcinomas in contrast to those of all normal livers, and 90% of cirrhosis showed no micronuclei. The micronuclei index showed a gradual increase during hepatocarcinogenesis and there was a significant increase between cirrhosis and low-grade dysplastic nodules, low-grade dysplastic nodules and high-grade dysplastic nodules, and highgrade dysplastic nodules and hepatocellular carcinomas. Telomere length showed a gradual shortening during hepatocarcinogenesis and a significant reduction was found in high-grade dysplastic nodules (P ¼ 0.024) and hepatocellular carcinomas (P ¼ 0.031) compared with normal and cirrhotic livers. The micronuclei index was correlated with telomere shortening (P ¼ 0.016). The p21 WAF1/CIP1 labeling index was significantly higher in cirrhosis than in normal livers (P ¼ 0.024) and markedly decreased in low-grade dysplastic nodules, high-grade dysplastic nodules, and hepatocellular carcinomas compared with cirrhosis (Po0.05). The p21 WAF1/CIP1 labeling index was associated with telomere length (Po0.001) but not micronuclei index. This study shows that telomere shortening, chromosomal instability, and inactivation of p21 WAF1/CIP1 checkpoint function occur in low-grade dysplastic nodules as well as in high-grade dysplastic nodules, and their cooperation is considered to be critical for malignant transformation during hepatitis B virus associated-multistep hepatocarcinogenesis.

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“…De Almeida et al 21 proposed that numerous BEs observed in the human liver with hepatitis C virus were due to viral infection. There are many viruses in the oral cavity that could be a source of induction of BEs if that is the case.…”

Section: Events In Exfoliated Human Cellsmentioning

confidence: 99%

Letters To The Editors

2006

Acta Cytologica

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Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma

Cited by 27 publications

References 31 publications

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Chromosomal instability, telomere shortening, and inactivation of p21WAF1/CIP1 in dysplastic nodules of hepatitis B virus-associated multistep hepatocarcinogenesis

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