EFFECT OF ALUMINUM-CHLORIDE ON MITOGENESIS, MITOSIS, AND CELL-CYCLE IN HUMAN SHORT-TERM WHOLE-BLOOD CULTURES - LOWER CONCENTRATIONS ENHANCEMITOSIS

Aluminum, the third most common element in the earth's crust (second t o oxygen and silicon) and recently suspected by some investigators to be implicated in Alzheimer disease etiology, has been studied in relat ion to its effect on mitogenesis, mitosis, and cell cycle. We have obs erved that 2-4 mM concentrations of AlCl3 have decreased the number of cells that undergo mitogenesis (PHA-induced blast transformation) and mitosis in human short term whole blood cultures. We have also shown that the rate of the cell cycle was slowed down, i.e., cell cycle time was increased in the presence of AlCl3. Also, we have demonstrated a reversible effect on aluminum-induced reduced mitotic index in long-te rm EBV-transformed lymphoblastoid cultures. Although safeguards such a s limiting aluminum serum concentrations have been recommended to prot ect individuals undergoing dialysis, it should be realized that concen tration accumulations of aluminum may increase over chronic exposures. Accordingly, if the number of cells stimulated by PHA is reduced in t he presence of AlCl3, there may be a reduction of immune competence, s ince the degree of PHA stimulation has been used as an indicator of im mune response. Similar reductions in mitotic index could affect every tissue involved with cell division. Although it may not be the same fo r higher concentrations, from our results, we have also shown that dec reased mitotic rates were reversible in long-term EBV-transformed lymp hoblastoid cultures. Increased numbers of mitoses were observed in hum an short-term whole blood cultures that were exposed to 2 muM concentr ations of aluminum chloride. The concentration is close to those found in normal human serum and within the ''safeguard'' range recommended for dialysis patients. A similar trend for aluminum sulfate was also o bserved, while preliminary results for three other aluminum species, l actate, citrate, and maltol, were also reported. Although previous rep orts have indicated a positive effect of aluminum on mitosis in vitro or in vivo, this is the first such report involving human material. It is clear that higher concentrations of aluminum chloride at 2.0-4.0 m M reversibly inhibit mitosis while more dilute concentrations of 1-2 m uM, closer to those found in normal serum, enhance mitosis. The presen t results, as well as those in the literature, suggest that aluminum m ay be an essential element in cellular processes for optimal growth, d evelopment, and health maintenance. Future research will further test this hypothesis. (C) 1994 Wiley-Liss, Inc.