Oxidative stress, hogg1 expression and NF-kappaB activity in cells exposed to low level chromium.
Chromium compounds are carcinogenic to the human lung, although the detailed biochemical mechanism is still unclear. To understand the carcinogenic mechanism in cells exposed to low level hexavalent chromium, we measured the generation of reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine (8-OH-dG), the transcription of hogg1, which encodes an 8-OH-dG repair protein, and NF-kappaB activation levels in the A549 human lung epithelial cell line after exposure to Cr (VI) at concentrations of 12.5 to 800 microM. In A549 cells, ROS levels and DNA binding by NF-kappaB increased in proportion to the concentration of Cr (VI). These increases were diminished by pretreatment with catalase, superoxide dismutase, or D-mannitol, but the levels of 8-OH-dG and expression of hogg1 did not change significantly with Cr (VI) exposure. These results suggest that the induction of ROS and the activation of NF-kappaB are important in the carcinogenic mechanism of Cr (VI), but it is unlikely that Cr (VI) concentrations below 800 microM increase 8-OH-dG levels or the expression of hogg1.
Kim
Yong-Dae
YD
Department of Preventive Medicine, College of Medicine, Chungbuk National University, 48 San Kaeshin-dong, Hungdok-gu, Cheongju, Chungbuk 361-763, South Korea.
An
Sung-Chul
SC
Oyama
Tsunehiro
T
Kawamoto
Toshihiro
T
Kim
Heon
H
D015152:Blotting, Northern; D002274:Carcinogens, Environmental / Q000506:poisoning*; D002460:Cell Line; D002857:Chromium / Q000506:poisoning*; D045647:DNA Glycosylases / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002274:Carcinogens, Environmental; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002857:Chromium; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human