Molecular mechanisms of nickel carcinogenesis.
Nickel treatment of intact cultured cells oxidized dichlorofluorescin to a fluorescent product indicating that nickel elevated the level of oxidants in cells. Nickel also caused an increase in crosslinking of amino acids to DNA and these complexes did not appear to involve the direct participation of Ni2+. Histidine, cysteine and tyrosine were prominent among the amino acids crosslinked to DNA. Nickel selectively damaged heterochromatin and this resulted in deletions of heterochromatic regions during nickel carcinogenesis. Thrombospondin was one of the genes expressed in normal cells that was not expressed in nickel-transformed cells. Other aspects of the molecular mechanism of nickel carcinogenesis are discussed.
New York University Medical Center, Nelson Institute of Environmental Medicine, NY 10016.
M
M
Costa
Z
Z
Zhuang
X
X
Huang
S
S
Cosentino
C B
CB
Klein
K
K
Salnikow
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D005452:Fluoresceins / Q000378:metabolism*; D017353:Gene Deletion; D006570:Heterochromatin / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000235:genetics; D009532:Nickel / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D019699:Thrombospondins
D000596:Amino Acids; D005452:Fluoresceins; D006570:Heterochromatin; D008562:Membrane Glycoproteins; D019699:Thrombospondins; C029569:diacetyldichlorofluorescein; D009532:Nickel; D004247:DNA