Selenoprotein deficiency enhances radiation-induced micronuclei formation.
The availability of selenium and the levels of specific selenoproteins might affect cancer risk by influencing the ability of DNA damaging agents to cause genomic instability and mutations. Transgenic mice that express reduced levels of selenoproteins and previously shown to be more susceptible to pathology associated with cancer development were used to study this possibility. These mice were exposed to X-rays and DNA damage assessed in the erythrocytes, where micronuclei formation was higher compared to the same cells obtained from irradiated wild-type controls. To determine whether the selenoprotein glutathione peroxidase-1 (GPx-1) might be involved in this protection, its levels were reduced by siRNA targeting in LNCaP human prostate cells. UV-induced micronuclei frequency was higher in these cells compared to control-transfected cells. These results indicate a role for selenoproteins in protecting DNA from damage and support human data implicating GPx-1 as a possible target of the chemoprotective effect of selenium.
Baliga
Manjeshwar S
MS
Department of Biotechnology, M.S. Ramaiah Institute of Technology, Bangalore, India.
Diwadkar-Navsariwala
Veda
V
Koh
Timothy
T
Fayad
Raja
R
Fantuzzi
Giamila
G
Diamond
Alan M
AM
D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D005979:Glutathione Peroxidase / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D048631:Micronucleus, Germline / Q000187:drug effects / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051140:Selenoproteins / Q000172:deficiency* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D014965:X-Rays; D000094765:Glutathione Peroxidase GPX1
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse