Role of mitochondria, ROS, and DNA damage in arsenic induced carcinogenesis.
The International Agency for Research on Cancer (IARC) declared arsenic a class I carcinogen. Arsenic exposure induces several forms of human cancers, including cancers of skin, lung, liver, and urinary bladder. The majority of the arsenic-induced cancers occur in skin. Among these, the most common is Bowen's disease, characterized by epidermal hyperplasia, full layer epidermal dysplasia, leading to intraepidermal carcinoma as well as apoptosis, and moderate dermal infiltrates, which require the participation of mitochondria. The exact mechanism underlying arsenic induced carcinogenesis remains unclear, although increased reactive oxidative stresses, leading to chromosome abnormalities and uncontrolled growth, and aberrant immune regulations might be involved. Here, we highlight how increased mitochondrial biogenesis and oxidative stress lead to mitochondrial DNA damage and mutation in arsenic induced cancers. We also provide therapeutic rationale for targeting mitochondria in the treatment of arsenic induced cancers.
Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung Taiwan.
Chih-Hung
CH
Lee
Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan and National Environmental Research Center, National Health Research Institutes, Zhunan, Taiwan, dermyu@nhri.org.tw.
Hsin-Su
HS
Yu
D000818:Animals; D001151:Arsenic / Q000633:toxicity; D020261:Arsenic Poisoning / Q000235:genetics* / Q000378:metabolism*; D001913:Bowen's Disease / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism
D001151:Arsenic