Antitumor Activity and Toxicity of Salts of Inorganic Group IIIa Metals: Aluminum, Gallium, Indium, and Thallium

Abstract

The Since gallium is a bone-seeking element (1-3), radionuclides of this element have been of clinical interest as diagnostic screening agents of bone tumors. In 1969 Edwards and Hayes (4) noted that carrier-free gallium-67 citrate was localized in addition in nonosseous tumors in patients with Hodgkin's disease and other lyinphomas. Deposition of this radioactive salt was also observed in patients with other "soft-tissue", slow-growing tumors (4-8), such as poorly differentiated thyroid adenocarcinoma, reticulum cell sarcoma, lymphosarcoma, and carcinomas of the lung, breast, colon, and kidney. These unexpected observations prompted studies on the concentration of this gallium radionuclide in various experimental animal tumors. Seven nonosseous rat and mouse carcinomas and sarcomas showed variable but distinct localization of 67Ga, in contrast to deposition in normal tissues (9). In addition, the Cancer Chemotherapy National Service Center has found that gallium nitrate possessed antitumor activity against Walker 256 carcinosarcoma in rats. These observations prompted us to examine the antitumor activity of gallium and metal salts chemically related to gallium. In increasing order of atomic numbers and atomic weight, the elements of Group lila of the periodic table are boron (B), aluminum (Al), gallium (Ga), indium (In), and thallium (Tl). The +3 oxidation state of these elements as cations is the most stable form in aqueous solution, except for thallium +3 which is slowly converted to the +1 form. The +3 forms of these elements were used in our experiments. We were unable to obtain a stable cationic

Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

“…Although previous reports have indicated that surface transferrin receptor density on HL-60 cells decreases during DMSO treatment (21,33) and that this decrease may precede by 24 In additional experiments, we studied the effect of agents that we hypothesized would be more specific in affecting transferrin receptor expression. Previous studies have shown that radioactive gallium was taken up avidly by certain tumors (41), and the use of gallium salts as an antitumor agent had been suggested a number of years ago (42). More recent studies suggest that the addition of transferrin potentiates gallium salt-mediated arrest of cellular proliferation (36), an effect that may be related to inhibition of iron uptake (37).…”

Aluminum in the Environment and Human Health

“…The intraperitoneal LD50 for Al(NO3)3 9H2O was reported to be 0.32 g/kg in male PBF1 mice and 0.33 g/kg in female Sprague-Dawley rats (481,482). The oral LD50 in rats has been reported to be 0.26 g/kg (176).…”

Metallomics related to gallium compounds: biochemical and xenobiochemical aspects

“…Regarding inorganic Ga compounds, it was observed that only the Ga 3+ cation has toxic activity. Thus, comparing the action of sulphates and chlorides, similar cytotoxic effects were evidenced [96].…”