Lead intoxication alters basal and parathyroid hormone-regulated cellular calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells.
The skeleton is the major reservoir of lead and calcium in humans, and plays an important role in systemic calcium regulation. Lead perturbs normal calcium transport and second messenger function, directly or indirectly, in virtually all cells studies so far. Therefore, we and others have postulated that an early and discrete toxic effect of lead is perturbation of one or more loci within the calcium messenger system. To understand further the role of lead on calcium homeostasis in bone, we undertook this study to characterize calcium homeostasis and the effect of lead on calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells, which exhibit the osteoblast phenotype. ROS cells were incubated in medium containing 45Ca for 20 hours. Monitoring the efflux of 45Ca from the cultures for 210 minutes allowed for the determination of kinetic parameters defining steady state calcium homeostasis. Three distinct intracellular kinetic calcium pools characterized 45Ca homeostasis. Treatment with either 400 ng parathyroid hormone (PTH)/ml culture medium for 1 hour or 25 microM lead for 20 hours increased total cell calcium. Treatment with PTH caused a larger increase of cell calcium in lead-intoxicated cells than either lead intoxication or PTH treatment alone. This increase suggests that lead may perturb normal calcium-mediated PTH responsiveness of the osteoblast. These experiments further establish a kinetic model for the study of calcium homeostasis in osteoblastic bone cells. The studies also advance the hypothesis that lead-induced perturbations of calcium-mediated processes represent an early effect of lead toxicity at the cellular level.
Long
G J
GJ
Department of Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Pounds
J G
JG
Rosen
J F
JF
D000818:Animals; D001859:Bone Neoplasms / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D002118:Calcium / Q000097:blood* / Q000502:physiology; D002132:Calcium Radioisotopes; D006706:Homeostasis / Q000502:physiology*; D007854:Lead / Q000009:adverse effects* / Q000378:metabolism; D007855:Lead Poisoning / Q000503:physiopathology*; D012516:Osteosarcoma / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D010280:Parathyroid Glands / Q000502:physiology*; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D002132:Calcium Radioisotopes; D007854:Lead; D002118:Calcium