Aluminum ions induce DNA synthesis but not cell proliferation in human fibroblasts in vitro.
The effect in vitro of aluminum (Al) ions on DNA synthesis and human dermal fibroblast proliferation using [Al] concentrations from 1.85 to 74 microM and incubation periods of 1, 2, 3, 4, and 5 d was assessed. The lowest concentration of Al that exerted a slight positive, although not significant, effect on DNA synthesis was 1.85 microM, after d 3 or 5 of incubation. The stimulating action of Al was more evident and statistically significant from concentrations of 3.7 microM and 2 d exposure onward. This Al-induced effect on [3H] thymidine incorporation into DNA increased in a time-dependent manner as [Al] in the culture medium rose, provoking increments of up to 322% above the control at [Al] 74 microM and 5 d incubation. In contrast, Al salts moderately increased fibroblast division in a continuous manner only from 7.4 to 74 microM after 3 d of incubation. Although significant overall, the minimal and inconstant mitogenic activity of Al differs greatly from and is not parallel to DNA synthesis, which is not clearly related to exposure times or Al concentrations. Abnormalities in Al-induced cellular metabolic processes described herein and their influence on the cell cycle may constitute a toxicity mechanism for human tissues, leading to disease development. Further studies are required to determine whether these findings can be extrapolated to in vivo situations.
Domínguez
Carmen
C
Biochemistry and Molecular Biology Center, Vall d'Hebron Hospitals, Barcelona, Spain.
Moreno
Antonio
A
Llovera
Marc
M
D000293:Adolescent; D000328:Adult; D000535:Aluminum / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008875:Middle Aged
D004247:DNA; D000535:Aluminum