Uptake of cadmium into cultured cells and its effects on cell growth and DNA synthesis are measured over a range of Cd concentrations of seven orders of magnitude. Cd uptake is found to be proportional to the external Cd concentration and to incubation time over a very broad range of concentrations. At least 200 mmol cadmium per kg dry weight of cells can be accumulated in this way, leading to exhaustion of the major intracellular Cd binding sites before cell death. On the other hand, very low cadmium concentrations down to 100 pM stimulate cell growth and DNA synthesis significantly. Stimulation is found in all three mammalian cell types examined: namely L6J1, a rat permanent myoblast cell line, LLC-PK1 porcine renal epithelial cells, and a primary rat chondrocyte culture. Cd acts as a cofactor with serum in L6J1 cultures, but is stimulatory only in serum-free cultures of chondrocytes. Stimulation occurs at Cd concentrations too low to result in a measurable induction of metallothionein. This might implicate the action of response amplifiers in the chain of events leading to Cd-stimulated DNA replication and cell growth.

Andrews
G.K.
(
1990
).
Regulation of metallothionein gene expression.
Progr. Food Nutrition Sci
14
,
193
258
Bonwick
G.A.
,
Fielden
P.R.
,
Davies
D.H.
) (
1991
).
Hepatic metallothionein levels in roach (rutilus rutilus L.) continuously exposed to water-borne cadmium.
Comp. Biochem. Physiol
99
,
119
125
Chibber
R.
,
Ord
M.
(
1990
).
Cadmium-induced multistep transformation of cultured indian muntjac skin fibroblasts.
Biol. Metals
3
,
213
221
Dagerlind
Å.
,
Schalling
M.
,
Eneroth
P.
,
Goldstein
M.
,
Hökfelt
T.
(
1990
).
Effects of reserpine on phenylethanolamine N-methyltransferase mRNA levels in rat adrenal gland: role of steroids.
Neurochem. Int
17
,
343
356
Gracia Cifone
M.
,
Alesse
E.
,
Procopio
A.
,
Paolini
R.
,
Morrone
S.
,
Di Eugenio
R.
,
Santoni
G.
,
Santoni
A.
(
1989
).
Effects of cadmium on lymphocyte activation.
Biochim. Biophys. Acta
1011
,
25
32
Jin
P.
,
Ringertz
N.R.
) (
1990
).
Cadmium induces transcription of proto-oncogenes c-jun and c-myc in rat L6 myoblasts.
J. Biol. Chem
256
,
14061
14064
Jin
P.
,
Sejersen
T.
,
Ringertz
N.R.
) (
1991
).
Recombinant platelet-derived growth factor-BB stimulates growth and inhibits differentiation of rat L6 myoblasts.
J. Biol. Chem
266
,
1245
1249
Kaji
T.
,
Mishima
A.
,
Yamamoto
C.
,
Sakamoto
M.
,
Koizumi
F.
(
1992
).
Effect of cadmium on the monolayer maintainance of vascular endothelial cells in culture.
Toxicology
71
,
267
276
Kang
Y.J.
,
Enger
M.D.
) (
1991
).
Cadmium inhibits EGF-induced DNA synthesis but increases cellular glutathione levels in NRK-49F cells.
Toxicology
66
,
325
333
Kishimoto
T.
,
Fukuzawa
Y.
,
Tada
M.
(
1990
).
Combined effect of cadmium (CdCl2) and high temperature on HeLa S3 cells.
Arch. Toxicol
64
,
383
386
Liu
J.
,
Kershaw
W.C.
,
Klaasen
C.D.
) (
1990
).
Rat primary hepatocyte cultures are a good model for examining metallothionein-induced tolerance to cadmium toxicity.
In Vitro Cell Develop. Biol
26
,
75
79
Lu
K.P.
,
Zhao
S.H.
,
Wang
D.S.
) (
1990
).
The stimulatory effect of heavy metal cations on proliferation of aortic smooth muscle cells.
Sci. China B
33
,
303
310
Makower
A.-M.
,
Wroblewski
J.
,
Pawlowski
A.
(
1988
).
Effects of IGF-I, EGF, and FGF on proteoglycans synthesized by fractionated chondrocytes of rat rib growth plate.
Exp. Cell Res
179
,
498
506
Nordlind
K.
(
1986
).
Further studies on the ability of different metal salts to influence the DNA synthesis of human lymphoid cells.
Int. Arch. Allergy Appl. Immunol
79
,
83
85
Ringertz
N.R.
,
Krohndal
U.
,
Coleman
J.R.
) (
1978
).
Reconstitution of cells by fusion of cell fragments.
Exp. Cell Res
113
,
233
246
Rubin
H.
(
1976
).
Nonspecific nature of the stimulus of DNA synthesis in cultures of chick embryo cells.
Proc. Nat. Acad. Sci. U.S.A
72
,
1676
1678
Scott
I.G.
,
Wolff
C.H.J.
,
Åkerman
K.E.O.
,
Andersson
L.C.
) (
1985
).
Effects of Cd upon Ca fluxes and proliferation in concavalin a-stimulated lymphocytes.
Exp. Cell Res
156
,
191
197
Searle
P.F.
,
Davison
B.L.
,
Stuart
G.W.
,
Wilkie
T.M.
,
Norstedt
G.
,
Palmiter
R.D.
) (
1984
).
Regulation, linkage, and sequence of mouse metallothionein I and II genes.
Mol. Cell. Biol
4
,
1221
1230
Sgagias
M.
,
Balter
N.J.
,
Gray
I.
(
1989
).
Uptake and subcellular distribution of cadmium in resting and mitogen-activated lymphocytes and its relationship to a metallothionein-like protein.
Environ. Res
49
,
262
270
Sundermann
F.W.
,
Barber
A.M.
) (
1988
).
Finger-loops, oncogenes, and metals.
Annals Clin. Lab. Sci
18
,
267
288
Tang
N.
,
Clapper
J.A.
,
Enger
M.D.
) (
1991
).
Cd inhibits EGF induced DNA synthesis but not EGF induced myc mRNA accumulation in serum starved NRK-49F cells.
Cell Biol. Toxicol
7
,
35
47
Thiele
D.J.
(
1992
).
Metal-regulated transcription in eukaryotes.
Nucl. Acids Res
20
,
1183
1191
von Zglinicki
T.
,
Marzabadi
M.
,
Roomans
G.M.
) (
1991
).
Water and ion distributions in myocytes cultured under oxidative stress mimic changes found in the process of aging.
Mech. Ageing Develop
58
,
49
60
Wroblewski
J.
,
Edwall
C.
(
1992
).
PDGF BB stimulates proliferation and differentiation in cultured chondrocytes from rat rib growth plate.
Cell Biol. Int. Rep
16
,
133
144
This content is only available via PDF.