Lead as a carcinogen: Experimental evidence and mechanisms of action

✍ Scribed by Ellen K. Silbergeld; Michael Waalkes; Jerry M. Rice

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 156 KB
• Volume: 38
• Category: Article
• ISSN: 0271-3586
• DOI: 10.1002/1097-0274(200009)38:3<316::aid-ajim11>3.0.co;2-p

✦ Synopsis

Recent epidemiological and experimental work con®rms 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 a-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-speci®c 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.