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

(G-to-T) trans-versions known to be induced
by 8-OHdG; this was interpreted as
strong evidence for the involvement of ROS
or reactive nitrogen species in crocidolite-
induced mutagenesis in vivo, consistent with
in vitro and cell-free studies [Unfried et al.
2002]. In contrast to glass fiber, crocidolite fiber
intratracheal instillation in rats increased
8-OHdG levels in DNA at one day and in its
repair enzyme activity at seven days. This in
vivo activity is consistent with asbestos- and
MMVF-induced increases of 8-OHdG oxidative
damage in vitro [Yamaguchi et al. 1999].
2.9.4.3.2 Membrane Interactions
Many mineral particles, elongate or not, can directly
cause membranolysis or other cytotoxic
responses without necessarily invoking extracellular
generation of ROS. Mechanisms of cell
damage by EMPs, independent of ROS formation,
have been proposed to involve direct interactions
of particle surface functional groups
(e.g., silicon or aluminum or magnesium) with
lipoproteins or glycoproteins of the cell membrane.
It has been suggested that silica particle
cytotoxicity to macrophages is due to distortion
and disruption of secondary lysosomal membranes
by phagocytosed particles whose surface
silanol groups hydrogen-bond to membrane
lipid phosphates, but that chrysotile-induced
cellular release of hydrolytic enzymes is due to
surface magnesium interacting ionically with
sialic acid residues of membrane glycoproteins,
inducing cation leakage and osmotic lysis [Allison
and Ferluga 1977]. Chrysotile fibers cause
lysis of red blood cells. EM indicates that cell
membranes become wrapped around the fibers
and that cell distortion and membrane
deformation correlate with an increase in the
intracellular ratio of sodium to potassium ions.
Cell pretreatment with neuraminidase prevents
fiber-cell binding, suggesting mediation
50
by cell membrane glycoproteins [Brody and Hill
1983]. However, chrysotile and crocidolite fibers
both induced increased membrane rigidity
in model unilamellar vesicles made of saturated
dipalmitoyl phosphatidylcholine (DPPC),
suggesting that lipid peroxidation is not involved
in membrane rigidity induced by asbestos
[Gendek and Brody 1990]. Silicate slate dust
and chrysotile fibers both induced hemolysis
in vitro and peroxidation of polyunsaturated
membrane lipids. However, poly(2-vinylpyridine
N-oxide) (PVPNO) and DPPC surface
prophylactic agents suppressed lysis but
not peroxidation, whereas SOD and catalase
did the reverse; and lysis was much faster than
peroxidation. This suggested that membrane lysis
and peroxidation are independent processes
[Singh and Rahman 1987]. However, either
mechanism may be involved in membrane damage
by EMPs; and seemingly disparate findings
suggest uncharacterized details of EMP properties
or of cellular or mineral conditioning under
test conditions may be important.
In in vitro studies, quartz dust and chrysotile
fibers induced loss of viability and release of lactate
dehydrogenase (LDH) from alveolar macrophages.
DPPC reduced these activities of the quartz but
not of the asbestos [Schimmelpfeng et al. 1992].
DPPC is adsorbed from aqueous dispersion
in approximately equal amounts on a surface
area basis, about 5 mg phospholipid per square
meter, by asbestos fibers [Jaurand et al. 1980]
and by nonfibrous silicate particles [Wallace
et al. 1992]; this is close to the value predicted
by mathematical modeling of an adsorbed bilayer
[Nagle 1993]. In the case of silica or clay
membranolytic dusts, this adsorption fully suppresses
their activity until toxicity is manifested
as the prophylactic surfactant is digested from
the particle surface by lysosomal phospholipase
enzyme; mineral-specific rates of the process
suggest a basis for differing fibrogenic potentials
NIOSH CIB 62 • Asbestos