Lead as a carcinogen: Experimental evidence and mechanisms of action

Recent epidemiological and experimental work confirms that inorganic lead c ompounds are associated with increased risks of tumorigenesis. In animals, these risks can be induced at doses that are not associated with organ toxi city and in mice that do not produce alpha-2 urinary globulin in the kidney . Thus the mechanisms of lead carcinogenicity are unlikely to be fully expl ained as toxicity-related sequelae of high dose exposure or as a rat-specif ic response involving overexpression of a renal protein. Plausible mechanis ms of lead carcinogenicity include direct DNA damage, clastogenicity, or in hibition of DNA synthesis or repair Lead may also generate reactive oxygen species and cause oxidative damage to DNA. Recent data indicate that lead c an substitute for zinc in several proteins that function as transcriptional regulators, including protamines, Lead further reduces the binding of thes e proteins to recognition elements in genomic DNA, which suggests an epigen etic involvement of lead in altered gene expression. These events may be of particular relevance in transplacental exposures and Inter cancer. Am. J. Ind. Med. 38:316-323, 2000. Published 2000 Wiley-Liss, Inc.(dagger)