Lead as a carcinogen: experimental evidence and mechanisms of action.
Recent epidemiological and experimental work confirms that inorganic lead compounds are associated with increased risks of tumorigenesis. In animals, these risks can be induced at doses that are not associated with organ toxicity 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 explained as toxicity-related sequelae of high dose exposure or as a rat-specific response involving overexpression of a renal protein. Plausible mechanisms of lead carcinogenicity include direct DNA damage, clastogenicity, or inhibition of DNA synthesis or repair. Lead may also generate reactive oxygen species and cause oxidative damage to DNA. Recent data indicate that lead can substitute for zinc in several proteins that function as transcriptional regulators, including protamines. Lead further reduces the binding of these proteins to recognition elements in genomic DNA, which suggests an epigenetic involvement of lead in altered gene expression. These events may be of particular relevance in transplacental exposures and later cancer.
Silbergeld
E K
EK
University of Maryland, Program in Human Health and the Environment, 10 South Pine Street, MSTF 9-36, Baltimore, Maryland 21201, USA.
Waalkes
M
M
Rice
J M
JM
D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced; D002273:Carcinogens / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000139:chemically induced; D007854:Lead / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology
D002273:Carcinogens; D007854:Lead