Asbestos Fibers and Other Elongate Mineral Particles: State of the ...

of different types of mineral particles [Wallace
et al. 1992].
Samples of intermediate-length and shortlength
NIEHS chrysotile were compared, with
and without DPPC lung surfactant pretreatment,
for micronucleus induction in Chinese
hamster lung V79 cells in vitro. Increase in
micronuclei frequency and multinuclear cell
frequency were induced by all samples, with
the greatest micronucleus induction by untreated
intermediate-length chrysotile fibers
and with greater activity for untreated versus
treated short chrysotile fibers. Cell viability
was greater for treated fibers [Lu et al. 1994].
NIEHS intermediate-length chrysotile was
mildly acid-treated to deplete surface-borne
magnesium while only slightly affecting fiber
length. Challenge of Chinese hamster lung fibroblast
cells in vitro for micronucleus induction
found no significant difference between
the treated and untreated samples, supporting
a model of chemically nonspecific chromosomal
and spindle damage effects [Keane et
al. 1999]. Chrysotile fiber induction of mucin
secretion in a tracheal cell culture was inhibited
by using lectins to block specific carbohydrate
residues on the cell surface; leached
chrysotile was inactive, suggesting that the surface
cationic magnesium of chrysotile was responsible
for interaction with cell surface
glycolipids and glycoproteins [Mossman et al.
1983]. However, complete removal of accessible
sialic acid residues from erythrocytes did not
inhibit hemolysis by chrysotile fibers, suggesting
that chrysotile fibers can induce lysis by interaction
with some other component of the cell
[Pelé and Calvert 1983].
2.9.4.3.3 Morphology-mediated Effects
A third possible mechanism for damage by EMP
principally involves morphology. The possibility
NIOSH CIB 62 • Asbestos
of frustrated phagocytosis is suggested by the
Stanton hypothesis of an overriding significance
of particle dimension for disease induction by
durable EPs. A general concept is that EMPs
longer than a phagocytic cell’s linear dimensions
cannot be completely incorporated in a
phagosome. Recruitment of membrane from the
Golgi apparatus or endoplasmic reticulum may
provide extensive addition to the plasma membrane
for a cell’s attempted invagination to accommodate
a long EMP in a phagosomal membrane
[Aderem 2002]. However, because of the
length of the EMP relative to the dimensions of
the cell, the final phagosomal structure is topologically
an annulus extending fully through the
cell, rather than an enclosed vacuole fully within
the cell. Following uptake of nonelongate particles,
there is a maturation of the phagosomal
membrane; the initial phagosomal membrane is
that of the cell’s external plasmalemma, which
cannot kill or digest phagocytosed material. After
sealing of the fully invaginated phagosomal
vesicle in the interior of the cell, there is a rapid
and extensive change in the membrane composition
[Scott et al. 2003]. This involves, in
part, an association with lysosomal vesicles
and exposure of particles within the secondary
phagosome or phagolysosome to lytic enzymes
and adjusted pH conditions. It is speculated
that failure of the phagosome to close, as occurs
in frustrated phagocytosis, induces dysfunction
of the system. Conventional phagocytosis
of nonelongate particles can lead to a respiratory
or oxidative burst of membrane-localized
NADPH oxidase of SO radicals, which may be
converted to H 2O 2, hydroxyl radicals, and other
toxic reactive products of oxygen. If these are
released extracellularly in connection with frustrated
phagocytosis, they are potentially harmful
to the tissue [Bergstrand 1990].
Failure of normal phagocytosis to be completed
may affect the duration or intensity
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