Magnesium inhibits nickel-induced genotoxicity and formation of reactive oxygen.
Nickel compounds are recognized to cause nasal and lung cancers. Magnesium is an effective protector against nickel-induced carcinogenesis in vivo, although its mechanisms of protection remain elusive. The effects of magnesium carbonate on the cytotoxicity and genotoxicity induced by nickel subsulfide were examined with respect to the inhibition of cell proliferation, micronuclei formation, DNA-protein cross-link formation, and intranuclear nickel concentration. The generation of reactive oxygen by nickel chloride was also analyzed by observing 8-hydroxy-deoxyguanosine formation from deoxyguanosine in the presence and absence of magnesium chloride. The suppression of up to 64% of the proliferation of BALB/3T3 fibroblasts by nickel subsulfide (1 microgram/ml) was reversed by magnesium. The nickel compound increased not only the number of micronuclei but also the amount of DNA-protein cross-links examined with CHO and BALB/3T3 cells, respectively. These genotoxic effects of nickel were again lessened by magnesium carbonate. In addition, the cellular accumulation of nickel increased 80-fold with nickel subsulfide treatment and decreased with magnesium carbonate treatment. Nickel also enhanced 8-hydroxy-deoxyguanosine formation in the presence of H2O2 and ascorbic acid, where magnesium played another suppressive role. In fact, inhibition by magnesium was still observed even in the absence of nickel treatment. These results suggest that the protective role of magnesium in nickel-induced cytotoxicity and genotoxicity can be attributed to its ability to reduce either the intracellular nickel concentration or reactive oxygen formation.
Hong
Y C
YC
Department of Preventive Medicine, Inha University Medical College, Inchon, Korea.
Paik
S R
SR
Lee
H J
HJ
Lee
K H
KH
Jang
S M
SM
D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D016466:CHO Cells; D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity*; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D006224:Cricetinae; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D017666:Deuterium Oxide / Q000737:chemistry; D005347:Fibroblasts; D066298:In Vitro Techniques; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology*; D009153:Mutagens / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002273:Carcinogens; D009153:Mutagens; D017382:Reactive Oxygen Species; D009532:Nickel; D003849:Deoxyguanosine; D008274:Magnesium; D017666:Deuterium Oxide; D001205:Ascorbic Acid; C017557:nickel subsulfide