On the mechanism of Cr (VI)-induced carcinogenesis: Dose dependence of uptake and cellular responses

Citation
Kj. Liu et al., On the mechanism of Cr (VI)-induced carcinogenesis: Dose dependence of uptake and cellular responses, MOL C BIOCH, 222(1-2), 2001, pp. 221-229
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR AND CELLULAR BIOCHEMISTRY
ISSN journal
0300-8177 → ACNP
Volume
222
Issue
1-2
Year of publication
2001
Pages
221 - 229
Database
ISI
SICI code
0300-8177(200106)222:1-2<221:OTMOC(>2.0.ZU;2-1
Abstract
Cr (VI) compounds are widely used industrial chemicals and are recognized h uman carcinogens. The mechanisms of carcinogenesis associated with these co mpounds remain to be investigated. The present study focused on dose-depend ence of Cr (VI)-induced uptake and cellular responses. The results show tha t Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 muM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin r esonance (ESR) trapping measurements showed that upon stimulation with Cr ( VI), A549 cells were able to generate reactive oxygen species (ROS). The am ount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cell ular parameters in a dose-dependent manner, (a) activation of nuclear trans cription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of tran scription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non -radioactive ELISA kit. At the concentration range used in the present stud y, no thresholds were found in all of these cell responses to Cr (VI). The results may guide further research to better understand and evaluate the ri sk of Cr (VI)-induced carcinogenesis at low levels of exposure.