Mechanism of action of nickel as a carcinogen: needed information.
It is generally accepted that cancer induction by organic compounds is a multistage process. Attempts to explain the carcinogenic action of nickel have been limited in scope, and centre around its interaction with nucleic acids, so that only one phase of the initiation process is emphasized. Other possible modes of action of nickel as a carcinogen have not received adequate attention. Classical initiation-promotion experiments employing nickel compounds as either the initiator or the promoter appear to be lacking. Also, little attention has been given to the possible indirect role of nickel as a stabilizer of free radicals formed by the oxidation of various unsaturated molecules including the dienes, cholesterol, and the well-known aromatic carcinogenic hydrocarbons. Other problems to be investigated include the role of nickel, if any, in the enhancement of the kinetics of the formation of ultimate carcinogens from the procarcinogen, or the possible inhibition of the biotransformation of active carcinogens into their inactive conjugates. It will be necessary at all times to carry out control experiments with the so-called inactive metal ions. Without experiments designed specifically to investigate the mechanism of action of nickel as a carcinogen, this topic will continue to remain in the realm of pure speculation.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002273:Carcinogens / Q000378:metabolism; D003043:Cocarcinogenesis; D004790:Enzyme Induction / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009532:Nickel / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D009696:Nucleic Acids / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009696:Nucleic Acids; D009532:Nickel; D006899:Mixed Function Oxygenases