[Nontargeted mutagenesis of plasmid pSP189 induced by nickel acetate and its relation with DNA damage in Vero cells].
OBJECTIVE
To detect the nontargeted mutagenesis and DNA damage in Vero cells induced by nickel acetate and to analyze their association, to provide clues to carcinogenic mechanism of nickel.


METHODS
Vero cells were treated with nickel acetate for 2.5 hours and cultivated in routine condition for 24 hours, and transfected with wild plasmid pSP189. Plasmid replicated in mammalian cells was collected and was transferred into E. coli MBM7070. The mutant was selected with special culture media. DNA damage in Vero cells was detected with modified single cell gel electrophoresis.


RESULTS
Nontargeted mutagenesis occurred in the cells pretreated with 250 mumol and 1,000 mumol nickel acetate, with mutagenesis frequencies of 9.46 x 10(-4) and 15.01 x 10(-4), 4.41 and 6.98 folds more as compared with the control group, respectively. Frequencies of DNA damage, DNA chain breaks, DNA-protein cross-links and DNA-DNA cross-links in all pretreated cells were significantly higher than those in the control group, but without dose-effect relationship. There was dose leap for mutagenesis frequencies and DNA-DNA cross-links.


CONCLUSIONS
Nickel acetate could induce nontargeted mutagenesis in the system of shuttle plasmid vectors, which could be related to DNA-DNA cross-links.
Ren
Z
Z
Department of Epidemiology, School of Public Health, Sun Yat-sen University of Medical Sciences, Guangzhou 510089, China.
Zhuang
Z
Z
Zhang
J
J
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D002522:Chlorocebus aethiops; D004249:DNA Damage / Q000187:drug effects*; D016296:Mutagenesis / Q000187:drug effects*; D009942:Organometallic Compounds / Q000633:toxicity*; D010957:Plasmids / Q000187:drug effects* / Q000235:genetics; D014709:Vero Cells
D000085:Acetates; D009942:Organometallic Compounds; C119536:nickel acetate