Molecular basis of arsenite (As⁺³)-induced acute cytotoxicity in human cervical epithelial carcinoma cells.
Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As(+3)) on DNA biosynthesis and cell death.



After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry.



We show that As(+3) ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As(+3) (7.5 µg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest.



Our results indicate that sudden exposure of cells to arsenite (As(+3)) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.
Department of Biological Sciences, Forman Christian College, Lahore, Pakistan.
Muhammad Nauman
MN
Arshad
Department of Microbiology, Government College University, Faisalabad, Pakistan; matif100@gmail.com.
Muhammad Atif
MA
Nisar
College of Allied Health Professionals, Directorate of Medical Sciences, Government College University, Faisalabad, Pakistan.
Mohsin
M
Khurshid
Department of Chemistry, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan.
Syed Zajif
SZ
Hussain
Agricultural Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
Umer
U
Maqsood
School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
Muhammad Tahir
MT
Asghar
Department of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
Jawad
J
Nazir
D017209:Apoptosis; D018053:Arsenites / Q000633:toxicity*; D015153:Blotting, Western; D002274:Carcinogens, Environmental / Q000009:adverse effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D000075322:Heavy Metal Poisoning; D006801:Humans; D007221:Industry; D008002:Libya; D011041:Poisoning; D016133:Polymerase Chain Reaction; D013723:Teratogens / Q000633:toxicity*; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology
D018053:Arsenites; D002274:Carcinogens, Environmental; D013723:Teratogens; C015001:arsenite
Pakistan; apoptosis; arsenite; caspases; cytotoxicity; epithelial carcinoma