Heavy metals are naturally occurring elements that have a high atomic weight and a density at least five times greater than that of water. Their multiple industrial, domestic, agricultural, medical, and technological applications have led to their wide distribution in the environment, raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. They are also classified as human carcinogens (known or probable) according to the US Environmental Protection Agency and the International Agency for Research on Cancer. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, genotoxicity, and carcinogenicity.

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Heavy metal toxicity and the environment.

This article reviews the effects of lead on genetic systems in the context of lead's various other toxic effects and its abundance and distribution in the environment. Lead is perhaps the longest used and best recognized toxic environmental chemical, yet it continued be used recklessly until only very recently. Lead is thus a lesson in the limitations and strengths of science, human conscience and common sense. Lead has been tested and found to be capable of eliciting a positive response in an extraordinarily wide range of biological and biochemical tests; among them tests for enzyme inhibition, fidelity of DNA synthesis, mutation, chromosome aberrations, cancer and birth defects. It reacts or complexes with many biomolecules and adversely affects the reproductive, nervous, gastrointestinal, immune, renal, cardiovascular, skeletal, muscular and hematopoietic systems as well as developmental processes. It is likely that lead is a selective agent that continues to act on and influence the genetic structure and future evolution of exposed plant and animal populations.

The genetic effects of environmental lead

Morphological transformation of Syrian hamster embryo cells was induced by direct exposure to some inorganic salts of nickel, cadmium, chromium, beryllium, and arsenic but not salts of iron, titanium, tungstate, zinc, aluminum, and nickel sulfide amorphous. Furthermore, no transformation was observed in untreated controls. Lethality, indicated by a reduction in cloning efficiency, occurred with carcinogenic and noncarcinogenic metal salts. In addition, transformation of Syrian hamster cells was observed also after transplacental exposure to inorganic salts of nickel, beryllium, chromate, and cadmium which had been injected into pregnant hamsters. The transformed colonies had a variety of morphologies reflecting the cell types present in early passages of cells and were identical to those observed after organic carcinogens. Animal experimental data exist for the carcinogenicity of all positive inorganic metals except arsenic. Epidemiological evidence indicates an association between exposures to all positive metals except for cadmium, although there is a possibility of a relationship between occupational exposure to cadmium and cancer of the prostate. Although in terms of dose-response relationships cadmium and chromium were the most potent transforming agents, the comparative potency of the various metals cannot be determined since it would depend on the ionization potential of the metal, the inorganic salt form, and possible biointeractions of the various metals.

https://cancerres.aacrjournals.org/content/canres/39/3/1008.full.pdf

Quantitative studies of in vitro morphological transformation of Syrian hamster cells by inorganic metal salts.

Thirty-eight metal salts were tested for their capacity to enhance transformation of Syrian hamster embryo cells by a simian adenovirus, SA7. All of the metal salts with known carcinogenic potential in animals or mutagenic activity in microbial or mammalian cells increased the SA7 transformation frequency. Metals were classified into three groups according to the concentration necessary to produce significant enhancement. Those showing highest activity (positive at less than 0.05 mM) were the salts of antimony, arsenic, cadmium, chromium, and platinum. The second group (positive from 0.05 to 0.6 mM) included beryllium, cobalt, copper, lead, manganese, mercury, nickel, silver, thallium, and zinc. Iron salts were placed in a third group (only positive at concentrations greater than 0.9 mM). With the exception of ZnCl2 and ZnSO4, enhancement was demonstrated by both a relative increase in the viral transformation frequency and an absolute increase in the number of transformed foci among treated cells. The latter observation and the demonstration of enhancement in the absence of overt cell killing negate the possibility that enhancement resulted from the selection of transformation-sensitive cells.

https://cancerres.aacrjournals.org/content/canres/39/1/193.full.pdf

Enhancement of Viral Transformation for Evaluation of the Carcinogenic or Mutagenic Potential of Inorganic Metal Salts

A review of the activity of metal compounds in mammalian cell transformation assays has been completed. Results from these assays appear to correlate well with the known carcinogenic activity displayed by specific metal compounds in vivo. Studies of cell transformation in vitro may provide information pertaining to the mechanism of the induction of carcinogenesis by certain metals.

In vitro assessment of the toxicity of metal compounds

In vitro neoplastic transformation of Syrian hamster cells by lead acetate and its relevance to environmental carcinogenesis

In vitro neoplastic transformation of Syrian hamster cells by lead acetate and its relevance to environmental carcinogenesis.

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In vitro neoplastic transformation of Syrian hamster cells by lead acetate and its relevance to environmental carcinogenesis.