Wh. Tolleson et al., APOPTOTIC AND ANTIPROLIFERATIVE EFFECTS OF FUMONISIN B-1 IN HUMAN KERATINOCYTES, FIBROBLASTS, ESOPHAGEAL EPITHELIAL-CELLS AND HEPATOMA-CELLS, Carcinogenesis, 17(2), 1996, pp. 239-249
Fumonisin B-1 is associated with various animal and human carcinomas a
nd toxicoses, including leukoencelphalomalacia, hepatocarcinoma, pulmo
nary edema and esophageal carcinoma, We have examined the cellular eff
ects of fumonisin B-1 in vitro using cellular model systems relevant t
o potential human target tissues, Although fumonisin B-1 has been desc
ribed as a mitogen in Swiss 3T3 cells based on stimulation of [H-3]thy
midine incorporation, in the current work it was found that fumonisin
B-1 inhibited incorporation of [H-3]thymidine by cultured neonatal hum
an keratinocytes and HepG2 human hepatocarcinoma cells at 10(-7) and 1
0(-4) M respectively, Fumonisin B-1 also inhibited clonal expansion of
normal human keratinocytes and HET-IA human esophageal epithelial cel
ls at 10(-5) M and growth in mass culture of normal human fibroblasts
at 10(-7) M. The clonogenicity of normal human keratinocytes decreased
to 45.5% of controls after exposure to 10(-4) M fumonisin B-1 for 2 d
ays, However, no differences in the cell cycle distribution of culture
d keratinocytes was noted after exposure to 10(-5) M fumonisin B-1 for
40 h., The viability of normal human keratinocytes and HET-1A cells d
ecreased as a result of fumonisin B-1 treatment, as determined by a fl
uorescein diacetate/propidium iodide flow cytometric cell viability as
say, Fumonisin B1-treated keratinocytes released nucleosomal DNA fragm
ents into the medium 2-3 days after exposure to 10(-4) M fumonisin B-1
and increased DNA strand breaks were detected in attached keratinocyt
es exposed to 0-10(-4) M fumonisin B-1 using a terminal deoxynucleotid
yl transferase-based immunochemical assay system, Furthermore, fumonis
in B-1-treated keratinocytes and HET-1A cells developed morphological
features consistent with apoptosis, as determined by phase contrast mi
croscopy, fluorescent microscopy of acridine orange stained cells and
electron microscopy, These results are consistent with the occurrence
of fumonisin B-1-mediated apoptosis in vitro.