Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals.
In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p<0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis.
Banerjee
Nilanjana
N
Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India. 2006.nilanjana@gmail.com
Banerjee
Mayukh
M
Ganguly
Sudipto
S
Bandyopadhyay
Santu
S
Das
Jayanta K
JK
Bandyopadhay
Apurba
A
Chatterjee
Mitali
M
Giri
Ashok K
AK
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D020261:Arsenic Poisoning; D001152:Arsenicals / Q000009:adverse effects*; D002453:Cell Cycle / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000097:blood; D012871:Skin Diseases / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D001152:Arsenicals; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c