Genetic toxicology of lead compounds.
We have investigated the activity of insoluble and soluble lead compounds in inducing mutagenesis, cell transformation and sister chromatid exchange in mammalian cells. Insoluble lead sulfide, readily phagocytized, was more than four times as toxic to V79 cells on a microM basis, than two moderately soluble lead compounds although the exposure time for the soluble salts was five times longer. These findings demonstrate the importance of different cellular mechanism(s) of metal uptake and bioavailability. Both insoluble lead sulfide and more soluble lead nitrate were mutagenic at the HPRT locus in V79 cells. Although less mutagenic at the higher concentrations, lead nitrate at a concentration of 500 microM enhanced the mutation frequency greater than 6-fold above background following a 5-day exposure. Although the mechanism(s) by which lead induces mutations is unknown, failure of both compounds to induce SCE and DNA single-strand breaks, detectable by alkaline elution, suggests that lead-induced mutations may not be a result of direct damage to DNA but may occur via indirect mechanisms including disturbances in enzyme functions important in DNA synthesis and/or repair, or in DNA-helical structure. Lead acetate also transformed SHE cells in a dose-response fashion following a 48-h exposure. Our results indicate that lead compounds may be genotoxic by an indirect mechanism, and lend support to the view that lead is a carcinogen.
Zelikoff
J T
JT
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Li
J H
JH
Hartwig
A
A
Wang
X W
XW
Costa
M
M
Rossman
T G
TG
D000818:Animals; D002273:Carcinogens; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007854:Lead / Q000494:pharmacology / Q000633:toxicity*; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D010587:Phagocytosis / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects
D002273:Carcinogens; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D007854:Lead; D007041:Hypoxanthine Phosphoribosyltransferase