Nickel potentiates the genotoxic effect of benzo[a]pyrene in Chinese hamster lung V79 cells.
The modulating effect of acute exposure to NiCl2 on the induction of chromosome aberrations by a model carcinogen, benzo[a]pyrene (B[a]P), was examined in Chinese hamster V79 lung cells. At concentrations up to 20 microg/ml (84.2 microM), NiCl2 did not significantly increase the frequency of chromosome aberrations in V79 cells when the cells were exposed concomitantly to 0.5 microg/ml B[a]P. Addition of the S15 liver microsomal fraction together with the B[a]P did not alter the results. Addition of NiCl2 2 hr before treatment of cells with 0.5 microg/ml B[a]P also did not result in a significant elevation of the frequency of chromosome aberrations, even at NiCl2 concentrations as high as 20 microg/ml. Contrasting sharply with these findings, when V79 cells were treated with NiCl2 immediately after B[a]P exposure, a significant increase in the frequency of chromosome damage was observed at NiCl2 concentrations as low as 5 microg/ml (21.1 microM). NiCl2-mediated enhancement of chromosome damage was also observed when V79 cells were exposed to the reactive B[a]P intermediate, benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE). In the BPDE-treated cells, the level of NiCl2-mediated enhancement was similar to that observed with the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (TPA, 100 ng/ml). These results are consistent with the view that the effect of nickel (II) on B[a]P-induced genetic damage is dependent on the relative times of exposure to Ni2+ and B[a]P. NiCl2 did not enhance the frequency of chromosome aberrations induced by Chromium (VI), regardless of the order of addition of the chemicals to the V79 cells. These results suggest that nickel may act as a promoter of chemically-induced genetic damage through induction of error-prone repair.
Deng
Cheng Z
CZ
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1019, USA.
Fons
Michael P
MP
Rosenblatt
Judah
J
El-Zein
Randa A
RA
Abdel-Rahman
Sherif Z
SZ
Albrecht
Thomas
T
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001580:Benzopyrenes / Q000633:toxicity; D002273:Carcinogens; D002460:Cell Line; D002857:Chromium / Q000737:chemistry; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015233:Models, Statistical; D009532:Nickel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D001580:Benzopyrenes; D002273:Carcinogens; D002857:Chromium; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C022838:nickel chloride; D009532:Nickel; D013755:Tetradecanoylphorbol Acetate