Effect of aluminum chloride on mitogenesis, mitosis, and cell cycle in human short-term whole blood cultures: lower concentrations enhance mitosis.
Aluminum, the third most common element in the earth's crust (second to oxygen and silicon) and recently suspected by some investigators to be implicated in Alzheimer disease etiology, has been studied in relation to its effect on mitogenesis, mitosis, and cell cycle. We have observed 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-term EBV-transformed lymphoblastoid cultures. Although safeguards such as limiting aluminum serum concentrations have been recommended to protect individuals undergoing dialysis, it should be realized that concentration accumulations of aluminum may increase over chronic exposures. Accordingly, if the number of cells stimulated by PHA is reduced in the presence of AlCl3, there may be a reduction of immune competence, since the degree of PHA stimulation has been used as an indicator of immune response. Similar reductions in mitotic index could affect every tissue involved with cell division. Although it may not be the same for higher concentrations, from our results, we have also shown that decreased mitotic rates were reversible in long-term EBV-transformed lymphoblastoid cultures. Increased numbers of mitoses were observed in human short-term whole blood cultures that were exposed to 2 microM concentrations of aluminum chloride.(ABSTRACT TRUNCATED AT 250 WORDS)
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
X L
XL
Yao
E C
EC
Jenkins
H M
HM
Wisniewski
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004854:Herpesvirus 4, Human; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology; D008938:Mitosis / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D010835:Phytohemagglutinins; D000077410:Aluminum Chloride