Metal interactions in carcinogenesis: enhancement, inhibition

Our plain-English summary of Metal interactions in carcinogenesis: enhancement, inhibition, by G.F. Nordberg, O. Andersen (Environmental Health Perspectives, 1981).

The study

• Authors: G.F. Nordberg, O. Andersen
• Journal: Environmental Health Perspectives
• Published: 1981;40:65-81
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Metals constitute a fundamentally important part of the total human environment. Since human exposure often involves complex mixtures of metal compounds and, possibly, organic compounds which may be carcinogenic per se, interactions between these compounds may add significantly to human cancer risk. Our present knowledge about these kinds of interactions is very limited. The best investigated area is benzo(a)pyrene (BP)-metal oxide particle interactions in respiratory carcinogenesis in the hamster. Metal oxide particles were also shown to modify the carcinogenic effect of nitrosamines. Several reports describe experiments in which selenium compounds exerted a generally anticarcinogenic and antimutagenic activity. Inorganic arsenic compounds, which are accepted to be carcinogenic in man, have so far been negative in animal experiments except for one recent suggested report. Several authors have, however, suggested that these compounds may act as cocarcinogens due to their inhibition of DNA repair, although animal experiments to demonstrate a cocarcinogenic effect of arsenic compounds have been negative so far, except for one preliminary report. The concentration of zinc in the diet seemed to influence both transplanted tumor growth and the carcinogenicity of several organic compounds, and the possibility of a correlation between dietary zinc and certain cancer forms in man has been suggested. Protection against development of Leydigiomas usually induced by cadmium injection was afforded by simultaneous injection of zinc salts. Nickel carcinogenesis has been reported to be antagonized by manganese, and synergism between Ni and organic carcinogens, e.g. BP, has been demonstrated. There is no firm evidence that lead may be a cocarcinogen, although some limited experimental evidence is available. Oxidizing agents have been demonstrated to increase, and reducing agents to antagonize, the mutagenic effect of chromium compounds in vitro. The content of carcinogenic and other metals in asbestos has been suggested to modify the carcinogenic properties of asbestos. Since much of the information available at present is suggestive, further research on these interactions as well as other possible interactions in metal carcinogenesis is needed. Studies should be made both in well defined in vitro systems and in relevant animal models.

In plain English

This 1981 article was a review, not a new study. The authors surveyed published animal experiments, laboratory (in vitro) studies and human studies on whether metals increase or decrease the cancer-causing or mutation-causing effects of other substances. It covered arsenic, selenium, zinc, nickel, lead, chromium and cadmium, and metal interactions with benzo(a)pyrene (BP), nitrosamines and asbestos. Among the studies reviewed, iron oxide, magnesium oxide and titanium oxide dusts strongly increased the cancer-causing activity of BP in hamsters. In one rat experiment, testicular tumors developed in 2 of 17 rats given cadmium plus zinc injections, compared with 21 of 25 rats given cadmium alone. In another, manganese dust lowered injection-site sarcomas from 39 of 40 rats given nickel subsulfide alone to 15 of 24. On asbestos, the authors noted that small amounts of metals, especially nickel, chromium, manganese and iron, are found with asbestos fibers, and that it has been suggested these metals might influence asbestos's cancer-causing properties. They concluded that more research is needed before this idea can be judged, and stated that much of the available information is suggestive.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: review of published experimental and epidemiological literature
• Who was studied: No new study population. The authors reviewed published experimental studies (animals, cultured cells, bacteria) and human epidemiological studies on metal interactions in cancer.
• Exposure: Metals and metal compounds (arsenic, selenium, zinc, nickel, lead, chromium, cadmium, manganese, metal oxide dusts) in combination with other carcinogens. For asbestos, the metals found with asbestos fibers: especially nickel, chromium, manganese and iron, with smaller amounts of vanadium, zinc, copper and cobalt. No asbestos fiber types were named.
• Main results:
  • In the hamster studies reviewed, iron oxide, magnesium oxide, titanium oxide and possibly other dusts strongly increased the cancer-causing activity of benzo(a)pyrene (BP) given into the windpipe.
  • In a reviewed rat experiment, 21 of 25 rats (88%) given a single cadmium injection had tumors after 10 months. In a second group given the same cadmium dose plus zinc acetate injections, 2 of 17 developed testicular tumors.
  • In a reviewed rat experiment, 15 of 24 rats given manganese dust with nickel subsulfide developed sarcomas at the injection site, compared with 39 of 40 rats given nickel subsulfide alone.
  • On asbestos, the review described a suggestion by another author (Cralley) that metals in asbestos fibers might influence the fibers' cancer-causing properties, with nickel and manganese discussed especially. The authors noted the current belief that asbestos carcinogenicity is closely related to fiber structure and size, and did not discuss that further.
  • The review described laboratory studies by Thomson and colleagues on how metal ions associated with asbestos affected the breakdown of BP by rat liver microsomes and the binding of BP to large molecules. Some ions stimulated and others inhibited these processes.
• The authors' conclusion: The authors concluded that an effect of metal ions associated with asbestos on the cancer process has been suggested, but that further research is needed before the plausibility of this hypothesis can be evaluated. More generally, they called for further research on metal interactions in well-defined in vitro systems and in relevant animal models.
• Limitations the authors state:
  • The authors stated that knowledge about these interactions is very limited.
  • The authors stated that much of the available information is suggestive.
  • The authors stated that only a few of the important metal combinations people are exposed to have been studied experimentally.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Carcinogenic.

Related studies

• Impact of effects of acid precipitation on toxicity of metals — G.F. Nordberg, R.A. Goyer, et al. (1985)
• Asbestos and metals as carcinogens — T. Norseth (1980)
• Occurrence of heavy metal-resistance in microflora from serpentine soil of Andaman — A. Pal, S. Dutta, et al. (2005)
• Metallic elements in crude and milled chrysotile asbestos from Quebec — C. Barbeau, M. Dupuis, et al. (1985)
• Metal contamination of Posidonia oceanica meadows along the Corsican coastline (Mediterranean) — C. Lafabrie, C. Pergent-Martini, et al. (2008)
• Chemical interaction: enhancement and inhibition of clastogenicity — W.A. Anwar (1993)

Browse more research in Environmental Health Perspectives, or return to medical research.