The genetic effects of environmental lead
Introduction
Lead is an abundant, globally well distributed, dangerous and important environmental chemical (Mahaffey, 1990a). Lead has been used since ancient times, and some its toxic effects have been recognized for several centuries. Rammazzini referred to lead poisoning in his 1713 work (Landrigan, 1990), and lead is believed to have contributed to the decline of Roman empire (Gilfillan, 1965). Lead's marvelously useful, and in some cases indispensable, properties have made it difficult, if not impossible to give up. Thus, humans have enjoyed its advantages and endured its harmful, and sometimes devastating effects, virtually since the dawn of civilization.
Even though many of the toxic effects of lead were known at the time, lead became used as a gasoline additive in the 1920s (Rosner and Markowitz, 1985); a victory for industry and business interests over environmental health. Serious atmospheric pollution with lead followed. But the war was not over. Science and medicine persisted, and in the last 30 years or so, the hazards of even very low lead-exposure levels have come to be widely accepted. Regulations governing uses and release into the environment have been instituted in many countries (although not all) around the world. Lead is among the top 10 US EPA priority pollutants (EPA, 1986a, EPA, 1986b).
At the same time, the US Food and Drug Administration has also fought to reduce or eliminate lead in a variety of products by stopping the use of lead solder in domestically produced food cans, and by taking steps to minimize or eliminate the use of lead in ceramicware, leaded crystalware, lead-containing bottled water, and lead capsules on wine bottles. These actions have also helped to decrease exposure to lead in the US (Bolger et al., 1996).
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Production and uses
Lead, today, remains an economically important commodity. The US consumed about 1 400 000 metric tons of lead in 1994 and the same in 1995. The largest amounts were used in storage batteries (1 220 000 metric tons) and ammunition (62 000 metric tons). Other uses were in bearing metals, cable covering, caulking, castings, pipes, sheet lead, solder and gasoline additives. About 250 000 metric tons were imported from other countries, mostly as ore, base bullion or as pigs and bars; 380 000 metric
Environmental lead
Lead concentrations in the surface waters of the eastern Arctic ocean were reported as 15 ng l−1 by Mart and Nürnberg (1984). At 1500 to 2000 m below the surface, the concentration was far less, 3–4 ng l−1. Closer to populated areas, concentrations are often higher than more isolated locations. North Atlantic and Norwegian sea surface waters show lead concentrations in the range of 29–41 ng l−1 (Mart and Nürnberg, 1984) and coastal waters can easily exceed 50 ng l−1 (Burnett et al., 1980).
Lead
Acute and chronic toxicity
In the US, acute lead poisoning seldom occurs in humans at the present time, but from past experience ingestion is known to result in colic, headache, cramps, muscle weakness, depression and coma and death in 1 to 2 days. In other countries of the world, lead poisoning occurs quite frequently. The third most common reported occupational disease in Taiwan, for example, is lead poisoning (Liou, 1994).
The main characteristics of chronic lead toxicity are a neuromuscular syndrome involving
Human carcinogenicity
Lead acetate and lead phosphate are listed as reasonably anticipated human carcinogens on the basis of rodent tests in the 7th annual report on carcinogens (ARC, 1994). The International Agency for Research on Cancer (IARC, 1987) lists inorganic lead compounds as 2B chemicals (possible human carcinogens), based primarily on rodent data. However, human epidemiological studies have revealed little evidence of a carcinogenic risk from even quite heavy exposures to lead compounds. Two studies which
Chromosome studies on human subjects
Gebhart (1984)reviewed studies of chromosome damage in cells of human subjects exposed to lead and other heavy metals. Methods are generally based on the microscopic analysis of mitotic metaphase chromosomes in short-term cultures of peripheral blood lymphocytes. Although several reports were published, results were mixed and the effects of lead, if any, were confounded with the effects of exposure to other metals in addition to lead, as well to the effects of smoking. O'Riordan and Evans (1974)
Other chromosome studies
Muro and Goyer administered 1% lead (acetate) in the diet of mice and found some chromosome damage evident in leukocytes.
Deknudt et al. (1977)administered lead acetate (0, 1.5, 6 or 15 mg) in the diet of cynomolgous monkeys for 16 months on normal or low calcium diet, and conducted chromosome analysis on cultured lymphocytes after 3, 10 and 16 months. There were no treatment-related increases in major chromosome abnormalities, except in the animals on the low calcium diet.
Léonard (1988)
Animal carcinogenicity studies
A number of animals studies have demonstrated that exposure to lead salts is capable of inducing cancer.
Kobayashi and Okamoto (1974)discovered that intratracheally administered lead oxide is cocarcinogenic with benzo[a]pyrene for the induction of lung tumors in Syrian hamster.
Azar et al. (1973)administered 10, 50, 100, and 500 ppm lead as lead acetate in the diet of rats for 2 years. A second 2-year feeding study utilized diets containing 0, 1000, and 2000 ppm lead as lead acetate. Lead-treated
In vitro mutation and other genetic toxicology tests
DiPaolo et al. (1978)reported that lead acetate induces cell transformation in Syrian hamster embryo cells and enhances the incidence of transformation induced by simian adenovirus. Casto et al. (1979)found lead oxide and lead chromate to enhance induction of transformation of Syrian hamster embryo cells by simian adenovirus.
Rossman et al. (1984)tested lead nitrate and six other metal compounds for the ability to induce λ prophage in Escherichia coli WP2s(λ). Lead nitrate showed the second
Genetics and biochemistry
In vitro, in the presence of lead chloride, DNA polymerase becomes more inaccurate and the frequency of incorporation of incorrect base pairs into newly synthesized DNA increases (Loeb and Mildvan, 1981; Zakour et al., 1981; Sirover and Loeb, 1976). Divalent ions of Be, Cd, Co, Cu, and Ni also have this effect. Lead (along with cadmium, copper and manganese) also decreases the fidelity of RNA synthesis catalyzed by RNA polymerase. It has been suggested that these ions may cause RNA synthesis to
Genetic adaptation and evolution
A number of plant species have demonstrated the ability to adapt to elevated levels of lead (and other toxic metals) in the environment. Advantage of this property has been taken for prospecting for metal containing deposits (Antonovics et al., 1971). Lead resistant plants that have been used as indicators include Tephrosia sp., Polycarpaea synandra, Gomphrena canescens (Cole, 1965), Alsine verna, Amorpha canescens, Rhus sp. and Sassafras sp. (Linstow, 1929). The highest concentration of lead
Adaptive mechanisms
Plants commonly synthesize small cysteine and glutathione rich peptides, known as phytochelatins, which sequester heavy-metal ions, apparently to keep them from interfering with sensitive critical functions (Grill et al., 1987, Grill et al., 1989). Cadmium (Tripathi et al., 1996), lead (Gupta et al., 1995), and probably other heavy metals induce increases in the concentrations of glutathione and phytochelatins (Scheller et al., 1987). The counterparts to phytochelatins in animals are the
Discussion and conclusions
As the foregoing illustrates, there are a large variety of toxic effects, attributable to lead exposure, which range from gastrointestinal, to muscular, to reproductive, to neurological and behavioral, to genetic. Though some research shows lead compounds are capable of inducing gene and chromosome mutations, lead is clearly not a powerful mutagen nor even a consistent mutagen among various test systems. The nervous system is very highly sensitive to the effects of lead, and at the lowest
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