Effects of methyl mercury on the cell cycle of primary rat CNS cells in vitro.
Methyl mercury (MeHg) may interfere with cell cycle progression in a number of ways, most notably through an inhibition of protein synthesis or through effects on mitotic spindle performance; both mechanisms have experimental support. Results from investigations into the effects of MeHg exposure on cell cycle progression in a primary fetal rat CNS culture are presented here. Colchicine was also investigated because it is a well-characterized mitotic inhibitor. Flow cytometric DNA content analysis was utilized to determine the cell cycle distribution histograms of control and treated cultures. In addition, a flow cytometric technique which involves the incorporation of 5-bromo-2'-deoxyuridine into newly synthesized DNA was used to discriminate between successive cell cycles. Exposure of the CNS cell cultures to MeHg (2 and 4 microM) over a period of 0-48 hr led to a G2/M-phase inhibition as determined by flow cytometric DNA content analysis. Whereas exposure to 2 microM MeHg resulted in G2/M-phase inhibition, an analysis of cell cycle progression demonstrated an inhibition of cell cycling through any phase following exposure to 4 microM MeHg; these effects occurred in the first round of cell division following plating. Exposure to colchicine (25 nM) resulted in a G2/M-phase arrest similar to that observed with MeHg (2 microM). However, a comparison of the cytotoxicity patterns between MeHg-treated and colchicine-treated cultures suggests that MeHg-induced cytotoxicity cannot be solely ascribed to G2/M-phase arrest, since at equivalent levels of G2/M-phase arrest, MeHg was more cytotoxic than colchicine. These results are consistent with the hypothesis that microtubules, and the mitotic spindle, are especially sensitive to MeHg exposure.
Ponce
R A
RA
Department of Environmental Health, University of Washington, Seattle 98195.
Kavanagh
T J
TJ
Mottet
N K
NK
Whittaker
S G
SG
Faustman
E M
EM
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003078:Colchicine / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D008767:Methylmercury Compounds / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D008767:Methylmercury Compounds; D004247:DNA; D003078:Colchicine