PMID- 25480871 OWN - NLM STAT- MEDLINE DCOM- 20160216 LR - 20150508 IS - 1464-3804 (Electronic) IS - 0267-8357 (Linking) VI - 30 IP - 3 DP - 2015 May TI - Precocious anaphase and expression of Securin and p53 genes as candidate biomarkers for the early detection in areca nut-induced carcinogenesis. PG - 381-9 LID - 10.1093/mutage/geu083 [doi] AB - Research over the years has generated enough evidence to implicate areca nut, as a carcinogen in humans. Besides oral, significant rise in the incidence of cancers of the oesophagus, liver and stomach was seen among areca nut chewers. Early diagnosis seems key to understand the initial processes of carcinogenesis which is highly curable. In North-East India, betel quid contains raw areca nut (RAN), lime and small portion of betel leaf without any other constituents. This study was not intended to isolate any active ingredients from the RAN and to look its action. The present objective is to validate the screening of precocious anaphase and analysis of expression of Securin and p53 in non-target cells like human peripheral blood lymphocytes (PBLs) and mouse bone marrow cells (BMCs) as early indicative parameters of RAN + lime-induced cancers. A total of 35 mice were examined at different time points for following ad libitum administration of RAN extract in drinking water with lime. Peripheral blood was collected from 32 human donors of which, 24 were RAN + lime heavy chewers. Expression of genes was assessed by immunoblotting and/or by immunohistochemistry. Histological preparation of stomach tissue of mice revealed that RAN + lime induced stomach cancer. A gradual increase in the frequency of precocious anaphases and aneuploid cells was observed in both RAN + lime-treated mouse BMC and human PBL of RAN heavy chewers. Levels of p53 and Securin were increased in these cells during early days of RAN + lime exposure. The level of Securin was significantly higher in human tumour samples than their adjacent normal counterpart. The expression of Securin was increased significantly in RAN + lime-administered mice as well as in stomach tumour. Present study revealed that precocious anaphase and expression of p53 and Securin in non-target cells are significantly associated with an increased risk of RAN-induced cancer and thus these parameters can be of early diagnostic value. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Kurkalang, Sillarine AU - Kurkalang S AD - Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong 793022, Meghalaya, India, Histopathology Division, Surgical Division and Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India. FAU - Banerjee, Atanu AU - Banerjee A AD - Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong 793022, Meghalaya, India, Histopathology Division, Surgical Division and Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India. FAU - Dkhar, Hughbert AU - Dkhar H AD - Histopathology Division. FAU - Nongrum, Henry B AU - Nongrum HB AD - Surgical Division and. FAU - Ganguly, Buddha AU - Ganguly B AD - Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong 793022, Meghalaya, India, Histopathology Division, Surgical Division and Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India. FAU - Islam, Mohammad AU - Islam M AD - Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India. FAU - Rangad, Gordon M AU - Rangad GM AD - Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India. FAU - Chatterjee, Anupam AU - Chatterjee A AD - Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong 793022, Meghalaya, India, Histopathology Division, Surgical Division and Otolaryngology and Head and Neck Surgery Department, Nazareth Hospital, Laitumkhrah, Shillong 793003, Meghalaya, India chatterjeeanupam@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141205 PL - England TA - Mutagenesis JT - Mutagenesis JID - 8707812 RN - 0 (Biomarkers, Tumor) RN - 0 (Carcinogens) RN - 0 (Plant Extracts) RN - 0 (Securin) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (pituitary tumor-transforming protein 1, human) SB - IM MH - Anaphase/drug effects MH - Animals MH - Areca/*chemistry MH - Biomarkers, Tumor/*genetics/metabolism MH - Carcinogenesis/drug effects MH - Carcinogens/*toxicity MH - Cells, Cultured MH - Early Detection of Cancer MH - Female MH - Gene Expression MH - Genomic Instability MH - Humans MH - Leukocytes, Mononuclear/drug effects/pathology MH - Male MH - Mice MH - Plant Extracts/*toxicity MH - Securin/*genetics MH - Tumor Suppressor Protein p53/*genetics EDAT- 2014/12/07 06:00 MHDA- 2016/02/18 06:00 CRDT- 2014/12/07 06:00 PHST- 2014/12/07 06:00 [entrez] PHST- 2014/12/07 06:00 [pubmed] PHST- 2016/02/18 06:00 [medline] AID - geu083 [pii] AID - 10.1093/mutage/geu083 [doi] PST - ppublish SO - Mutagenesis. 2015 May;30(3):381-9. doi: 10.1093/mutage/geu083. Epub 2014 Dec 5.