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Title: Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells

Abstract

Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus, an interaction between arsenic and cigarette smoking in lung carcinogenesis was suspected. p53 dysfunction or mutation in lung epithelial cells was frequently observed in cigarette smokers. Our present study was to explore the differential effects by arsenic on H1355 cells (human lung adenocarcinoma cell line with mutation in p53), BEAS-2B (immortalized lung epithelial cell with functional p53) and pifithrin-{alpha}-treated BEAS-2B cells (p53-inhibited cells). These cells were treated with different doses of sodium arsenite (0, 0.1, 1, 5 and 10 {mu}M) for 48 h. A greater reduction in cell viability was observed in the BEAS-2B cells vs. p53 compromised cells (H1355 or p53-inhibited BEAS-2B). Similar observation was also made on 7-day cell survival (growth) study. TUNEL analysis confirmed that there was indeed a significantly reduced arsenite-induced apoptosis found in p53-compromised cells. Centrosomal abnormality has been attributed to eventual chromosomal missegregation, aneuploidy and tumorigenesis. In our present study, reduced p21 and Gadd45a expressions and increased centrosomal abnormality (atopic and multiple centrosomes) were observed in both arsenite-treated H1355 and p53-inhibited BEAS-2B cells as compared with similarly treated BEAS-2B cells.more » Increased anchorage-independent growth (colony formation) of BEAS-2B cells co-treated with pifithrin-{alpha} and 5 {mu}M sodium arsenite was also observed in soft agar. Our present investigation demonstrated that arsenic would act specifically on p53 compromised cells (either with p53 dysfunction or inhibited) to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenic, especially under the condition of p53 dysfunction.« less

Authors:
;  [1];  [2];  [3];  [4]
  1. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan (China)
  2. Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
  3. Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
  4. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan (China), E-mail: 406lwchang44@yahoo.com
Publication Date:
OSTI Identifier:
21077863
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 225; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2007.07.017; PII: S0041-008X(07)00332-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGAR; ANEUPLOIDY; APOPTOSIS; ARSENIC; CARCINOGENESIS; CARCINOMAS; COLONY FORMATION; DNA DAMAGES; GENES; HEALTH HAZARDS; LUNGS; MONOCLINIC LATTICES; RESPIRATORY TRACT CELLS; SODIUM

Citation Formats

Liao Weiting, Lin Pinpin, Cheng, T.-S., Yu, H.-S., and Chang, Louis W. Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.07.017.
Liao Weiting, Lin Pinpin, Cheng, T.-S., Yu, H.-S., & Chang, Louis W. Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells. United States. doi:10.1016/j.taap.2007.07.017.
Liao Weiting, Lin Pinpin, Cheng, T.-S., Yu, H.-S., and Chang, Louis W. Sat . "Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells". United States. doi:10.1016/j.taap.2007.07.017.
@article{osti_21077863,
title = {Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised human lung cells},
author = {Liao Weiting and Lin Pinpin and Cheng, T.-S. and Yu, H.-S. and Chang, Louis W.},
abstractNote = {Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus, an interaction between arsenic and cigarette smoking in lung carcinogenesis was suspected. p53 dysfunction or mutation in lung epithelial cells was frequently observed in cigarette smokers. Our present study was to explore the differential effects by arsenic on H1355 cells (human lung adenocarcinoma cell line with mutation in p53), BEAS-2B (immortalized lung epithelial cell with functional p53) and pifithrin-{alpha}-treated BEAS-2B cells (p53-inhibited cells). These cells were treated with different doses of sodium arsenite (0, 0.1, 1, 5 and 10 {mu}M) for 48 h. A greater reduction in cell viability was observed in the BEAS-2B cells vs. p53 compromised cells (H1355 or p53-inhibited BEAS-2B). Similar observation was also made on 7-day cell survival (growth) study. TUNEL analysis confirmed that there was indeed a significantly reduced arsenite-induced apoptosis found in p53-compromised cells. Centrosomal abnormality has been attributed to eventual chromosomal missegregation, aneuploidy and tumorigenesis. In our present study, reduced p21 and Gadd45a expressions and increased centrosomal abnormality (atopic and multiple centrosomes) were observed in both arsenite-treated H1355 and p53-inhibited BEAS-2B cells as compared with similarly treated BEAS-2B cells. Increased anchorage-independent growth (colony formation) of BEAS-2B cells co-treated with pifithrin-{alpha} and 5 {mu}M sodium arsenite was also observed in soft agar. Our present investigation demonstrated that arsenic would act specifically on p53 compromised cells (either with p53 dysfunction or inhibited) to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenic, especially under the condition of p53 dysfunction.},
doi = {10.1016/j.taap.2007.07.017},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 225,
place = {United States},
year = {Sat Dec 01 00:00:00 EST 2007},
month = {Sat Dec 01 00:00:00 EST 2007}
}