Lead inhibits growth and induces apoptosis in normal rat fibroblasts.
The effects on normal rat fibroblasts of lead supplementation (as lead acetate) in the medium were examined. The amount of lead acetate ranged from 0.078 microM to 320 microM, at 14 concentrations. The normal level of lead in the medium was 0.060 microM, and the normal concentration of lead in the fibroblasts was 3.1 +/- 0.1 ng/10(7) cells: these represented the control conditions. On studying fibroblast proliferation and survival after incubation for 48 hours, a lead acetate dose-dependent inhibition of cell proliferation was observed, the results being shown to be significant by ANOVA (p < 0.01), and suggesting a significant dose-response relationship. Apoptosis, evaluated by quantifying cytoplasmic DNA fragments, differs significantly between the lead levels tested. The distribution in the cell cycle, evaluated by using a fluorescence-activated cell sorter, showed a dose-dependent accumulation of cells in the G0/G1 phase, with a compensatory decrease in the percentage of cells in the S phase. Moreover, the occurrence of a subdiploid peak confirmed that apoptosis was more evident when the medium was supplemented with lead acetate at concentrations of 5-20 microM. The inhibition of cell growth is probably due to a direct inhibition of cell proliferation.
Iavicoli
I
I
Institute of Occupational Health School of Medicine, Catholic University of S. Cuore, Largo Francesco Vito, 00168 Rome, Italy.
Carelli
G
G
Sgambato
A
A
Masci
O
O
Ardito
R
R
Cittadini
A
A
Castellino
N
N
D000826:Animal Testing Alternatives; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D009942:Organometallic Compounds / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D013054:Spectrophotometry, Atomic
D017077:Culture Media, Conditioned; D009942:Organometallic Compounds; D004247:DNA; C008261:lead acetate