Effects of methylmercury and mercuric chloride on differentiation and cell viability in PC12 cells.
The effects of methylmercury (CH3Hg) or mercuric chloride (HgCl(2)) on neurite outgrowth and cell viability were quantified using undifferentiated (unprimed) and differentiated (primed) pheochromocytoma (PC12) cells. In unprimed cells, following 24-h exposure, CH3Hg significantly decreased NGF-stimulated neurite outgrowth at concentrations of 0.3-3 microM. However, HgCl(2) significantly increased both neurite outgrowth and the number of branch points, a component of neurite outgrowth. In primed PC12 cells, following 24-h exposure, both CH3Hg and HgCl(2) inhibited NGF-stimulated neurite outgrowth with an EC(50) of approximately 0.03 microM; however, there was a difference between CH3Hg and HgCl(2) effects on the subcomponents of total neurite outgrowth. CH3Hg significantly decreased both the number of branch points (0.3 microM) and fragment length (0.01 microM), while HgCl(2) only decreased fragment length (0.03 microM). Cell viability was assessed in the same cultures by trypan-blue exclusion. In unprimed cells, the EC(50) for cytotoxicity of CH3Hg in the presence and absence of NGF was 0.21 +/- 0.04 and 0.87 +/- 0.12 microM, respectively, and for HgCl(2) in the presence and absence of NGF was 8.18 +/- 1.52 and 5.02 +/- 0.74 microM, respectively. In primed cells, the EC(50) for cytotoxicity of CH3Hg in the presence or absence of NGF was 1.17 +/- 0.38 and 0.73 +/- 0.14 microM, respectively, and for HgCl(2) in the presence or absence of NGF was 3.96 +/- 0.82 and 3.81 +/- 0.91 microM, respectively. In the primed PC12 model, cytotoxicity occurred at concentrations that were at least 30-fold higher than the EC(50) for neurite outgrowth, suggesting that the mercurial compounds can act selectively on the process of differentiation.
Parran
D K
DK
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Mundy
W R
WR
Barone
S
S
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D018715:Microscopy, Video; D009414:Nerve Growth Factors / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D016716:PC12 Cells; D051381:Rats
D008767:Methylmercury Compounds; D009414:Nerve Growth Factors; D008627:Mercuric Chloride