Osseous and Intestinal Compartments in the Humoral Hypercalcemia of Malignancy Associated to Walker 256 Tumor in Rats

Abstract

The objective of the present work has been to study some aspects of bone and intestinal compartments in rats with Walker 256 carcinosarcoma, an experimental model of humoral hypercalcemia of malignancy (HHM). The results have been compared to those obtained in control animals and, also, to those obtained in Yoshida sarcoma-bearing rats, which were used as tumoral controls without hypercalcemia. Urinary hydroxyproline/creatinine ratio (OHProl/creat) is increased, in both Walker 256 and Yoshida tumor-bearing animals, showing the nonspecifity of this bone marker. However, serum tar-trate-resistant acid phosphatase (TRAP) levels are increased in Walker 256 tumor-bearing animals, but they are normal in Yoshida tumor-bearing animals, indicating that TRAP is a better index of bone resorption than OHProl/ creat in the HHM syndrome. The decrease of bone calcium content in Walker 256 tumor-bearing rats, not shown by Yoshida-bearing rats, also reflects an increased bone resorption due to HHM. Serum and bone osteocalcin levels are similar in control, Walker 256 and Yoshida tumor-bearing rats, but we observed a decrease in serum alkaline phosphatase levels in Walker 256 and Yoshida tumor-bearing animals, which could also be a nonspecific tumor effect, due to the presence of the neoplasia. Our results support the convenience of the employment of a nonhypercalcemic tumor group as control in the HHM study, in addition to the healthy controls. We have also observed higher 1,25-dihydroxyvitamin D serum levels in Walker 256 tumor-bearing rats than in control and Yoshida tumor-bearing rats. On the other hand, we have found normal levels in the fractional rate of intestinal calcium absorption in Walker-256 tumor-bearing rats, in spite of their high calcium levels, and a significant decrease of this parameter in Yoshida sarcoma-bearing animals. These results support the concomitant contribution of intestinal compartment to hypercalcemia, in the experimental model of HHM studied.

Effects of Parathyroid Hormone Related Peptide (1 - 34) and 1,25-Dihydroxyvitamin D on Bone Alkaline Phosphatase Activity in Fetal Rat Calvaria Cultures

“…This system has osteoblast and osteoclast cell lines and it also preserves some aspects of the skeletal microenvironment. Concentration of 1,25(OH)2D3 was selected according to our resuits (Table 1) and PTH and PTHrP concentrations were selected according to previous results (Torres, de Ia Piedra and Rapado 1993: In these experiments, the initial culture medium containing BSA was removed, and substituted by another without BSA when the agonists were added, due to the possible binding of the l,25(OH)2D3 to the albumin that reduces the free fraction of vitamin D metabolite, the active form.…”

Animal Models of Cancer-Associated Hypercalcemia

“…Tumor-bearing rats had decreased calcium content in their bones secondary to PTHrP-mediated osteolysis [ 181 ]. Despite high serum calcium levels, the rats had a normal fractional rate of intestinal calcium absorption, suggesting an intestinal contribution to the hypercalcemia [ 182 ]. This model demonstrated a role of the TGF-β-PTHrP axis in HHM.…”

Usefulness of Serum Pyridinoline Cross-Linked Carboxy-Terminal Telopeptides of Type I Collagen and Osteocalcin in the Study of the Bone Resorption Rate in Oophorectomized Rats

“…Until recently, the possibilities to determine biochemical bone markers in the rat model were limited to alkaline-or tartrate-resistant acid phosphatases, colorimetric methods based on the hydrolysis of p-nitrophenyl phosphate [8,9], and urinary hydroxyproline [10], a colorimetric method based on the technique of Kivirikko [11]. A few years ago, antibodies against rat osteocalcin (BGP) were developed, and this biochemical marker of bone formation could also be determined in rats [12,13].…”